Sulfur mustard (SM) is a lipophilic vesicant alkylating agent. It can be absorbed into the body via multiple routes, including the respiratory tract, cornea, and skin, leading to systemic organ damage. The alkylation of DNA, proteins, and nucleic acids by SM produces unique cytotoxicity, and SM is also a potent mutagen and carcinogen. Regardless of the exposure route, the lung is the most vulnerable target organ. Acute respiratory distress syndrome and pulmonary infections are the primary causes of early mortality in SM poisoning. To date, no specific antidote is available for SM. This review aims to discuss the cellular and molecular mechanisms of acute and delayed SM-induced pulmonary injury, with emphasis on DNA damage, oxidative stress, inflammatory response, and apoptosis mechanisms. These mechanisms indicate the potential application of anti-DNA damage, antioxidant, anti-inflammatory, and anti-apoptotic therapies to help mitigate SM-induced pulmonary injuries.

Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, the cellular mechanisms driving SM-induced apoptosis remain poorly understood. This study seeks to elucidate the apoptotic pathways involved in SM-induced pulmonary injury using a rat model. We induced acute lung injury through two delivery methods: intraperitoneal injection (8 mg/kg) and intratracheal instillation (2 mg/kg) of SM, with both doses representing 1 LD50. We assessed apoptosis-related proteins and gene expression through TUNEL staining, immunohistochemistry, and quantitative real-time PCR analyses. Intraperitoneal administration of SM resulted in significantly elevated expression of apoptotic markers including annexin A1, annexin A2, cytochrome C, caspase-12, and JNK3, in alveolar epithelial cells compared to intratracheal delivery. Both TUNEL assays and immunohistochemical staining confirmed these findings. These results indicate that intraperitoneal SM exposure triggers more severe apoptotic responses in alveolar epithelial cells than intratracheal exposure at equivalent doses. These findings demonstrate that intraperitoneal models can effectively identify apoptosisrelated molecular targets suitable for therapeutic development.

Sulfur mustard (SM), a highly reactive alkylating agent, remains a significant threat to both military personnel and civilian populations due to its toxic effects. Although substantial research has been conducted, the precise apoptotic mechanisms triggered by SM exposure are not yet fully understood. This study aimed to assess potential differences in the apoptosis following SM-induced acute pulmonary injury via the two routes. An acute pulmonary injury model was developed using SM at an equitoxic dose (1 LD50), administered via either a single intraperitoneal injection or intratracheal instillation. Protein expression levels and mRNA expressions of cysteinyl aspartate specific proteinase-2 (caspase-2), caspase-4, caspase-7, caspase-8, p53, and factor-associated suicide ligand (FasL) were evaluated using immunohistochemistry labeling and polymerase chain reaction analysis. At equitoxic doses, the intraperitoneal SM group exhibited significantly higher protein expression ratios and mRNA expression levels of caspase-2, caspase-4, caspase-7, caspase-8, p53, and FasL in the epithelial cells of the alveolar septa from the right lower lobe of the rat’s lungs than the intratracheal SM group. Both protein and mRNA expression levels increased progressively over time in both groups. The findings indicate that SM in early-phase induces apoptosis through intrinsic and extrinsic pathways as well as possible endoplasmic reticulum stress-related pathway. These insights contribute to a deeper understanding of SM toxicity and offer a basis for developing targeted therapeutic strategies to mitigate its harmful effects.

Objectives:Pathomechanisms of sulfur mustard (SM) are not fully understood, and no specific medical countermeasures exist to prevent SM-induced pulmonary injury. This study aimed to evaluate the apoptosis following SM-induced acute pulmonary injury. Materials and Methods:Acute pulmonary injury models were established using SM at an equivalent toxicity dose (1 LD50), administered via intraperitoneal injection or intratracheal instillation. Protein expression levels and mRNA expressions of apoptosis-related markers, including cellular inhibitor of apoptosis proteins-1 and -2 (cIAP-1, cIAP-2), Fas, Bcl-2-associated death promoter (Bad), second mitochondria-derived activator of caspases (Smac), and survivin (BIRC5), were analyzed using immunohistochemistry and polymerase chain reaction. Results:The intraperitoneal SM group exhibited significantly higher levels of apoptotic cells in the alveolar septa and increased protein and mRNA expression of cIAP-1, cIAP-2, Fas, Bad, Smac, and BIRC5 compared to the intratracheal SM group. These changes displayed a time-dependent increase in both protein and gene expression levels. Conclusion:SM-induced pulmonary injury involves both extrinsic (Fas, cIAP-1, cIAP-2) and intrinsic (Bad, Smac) pathways as well as caspase-dependent pathways (BIRC5). These findings provide valuable insights into the underlying mechanisms of SM toxicity and may facilitate the development of targeted therapeutic strategies.

Sulfur mustard (SM) is a highly toxic bifunctional alkylating agent that inflicts severe damage on the respiratory tract. Although numerous studies have examined the mechanisms underlying SM-induced pulmonary injury, the exact pathways involved remain unclear. This study aims to investigate an acute pulmonary injury model, with SM administered as a single intraperitoneal injection (8 mg/kg) or single intratracheal instillation (2 mg/kg) at equal toxicity doses (1LD50). The results revealed that epithelial cells in the alveolar septa of the intraperitoneal SM group exhibited a significantly higher expression of apoptotic markers, including pro-apoptotic protein Bax, caspase-3, and caspase-9 proteins, than those in the tracheal SM group. Conversely, the expression of the anti-apoptotic protein Bcl-2 was significantly lower in the intraperitoneal SM group than in the tracheal SM group, as confirmed by TUNEL staining and immunohistochemical staining. The intraperitoneal SM group exhibited markedly higher expression of fibrosis-related proteins, including MMP-2, MMP-9, TIMP-1, TIMP-2, collagen type I, collagen type III, TGF-β1, and Smad7, than the tracheal SM group. These markers, detected through immunohistochemical immunolabeling, indicate a more significant fibrotic response in the intraperitoneal group. In summary, this study demonstrates that intraperitoneal exposure to SM results in increased apoptosis, elevated expression of pro-apoptotic proteins, and fibrosis-related proteins in the alveolar epithelial cells compared with intratracheal exposure, even at equivalent toxicity levels. Our findings highlight the suitability of the intraperitoneal route for further investigation and identify apoptotic and fibrosis-related proteins as potential targets for intervention in SM-induced pulmonary injury.

Objective Sulfur mustard (SM) is an important chemical warfare agent. The mechanisms underlying SM toxicity have not been completely elucidated. However, oxidative stress and the subsequent damage to macromolecules have been considered ascrucial steps in SM toxicity. In this study, a rat model of SM-induced acute pulmonary injury was established using an equal toxicity dose (1LD50). This study employed two methods to directly compare oxidative stress indices in serum enzymes and the epithelial cells of the alveolar septa. Methods Male Sprague-Dawley rats were randomly divided into intraperitoneal SM, intraperitoneal propylene glycol control, tracheal SM, tracheal propylene glycol control, and control groups. SM-induced serum enzyme levels and protein expression in the epithelial cells of the alveolar septa were measured using enzyme-linked immunosorbent assay and immunohistochemistry. Results Serum levels of superoxide dismutase, catalase, and glutathione peroxidase were upregulated in the intraperitoneal SM group compared with those in the tracheal SM group. Positive expression ratios of CuZn-superoxide dismutase, Mn-superoxide dismutase, paraoxonase-1, and apolipoprotein-1 proteins in the epithelial cells of the alveolar septa in the intraperitoneal SM group were elevated compared with those in the tracheal SM group. Conclusion Under SM (1LD50) exposure, there were significantly higher serum enzyme levels and protein expressions in the epithelial cells of the alveolar septa of rats injected with SM intraperitoneally compared with SM administered by intratracheal instillation. The results demonstrated that the differences in oxidative stress indices at the molecular level in SM-induced pulmonary injury were dependent on the route of exposure.

Objective: Sulfur mustard (SM) is an important chemical warfare agent. The mechanisms underlying SM toxicity have not been completely determined. However, oxidative stress and the following damage to macromolecules have been considered one of the crucial steps in SM toxicity. In the current study, an animal model of SM was established by equal toxicity dose (1LD50)-induced acute pulmonary injuries in rats. This study used two methods to directly compare oxidative stress indices in serum enzymes and alveolar septum. Methods: Male Sprague-Dawley rats were randomly divided into intraperitoneal SM, intraperitoneal propylene glycol, tracheal SM, tracheal propylene glycol, and normal groups. SM-induced serum enzyme levels and protein-related expression in the alveolar septum were measured by ELISA and immunohistochemistry methods. Results: Serum SOD, CAT, and GSH-Px levels were increased in the intraperitoneal SM group, compared with the tracheal SM group. Positive expression ratios of CuZn-SOD, Mn-SOD, PON-1, and ApoA1 proteins in the alveolar septum of the intraperitoneal SM group were increased, compared with the tracheal SM group. Conclusion: Under SM (1LD50), there were significantly higher serum enzyme levels and protein-related expression levels in the alveolar septum of rats injected with SM intraperitoneally, compared with SM administered by intratracheal instillation. Differences in oxidative stress indices associated with SM (1LD50)-induced pulmonary injuries at the molecular level are dependent on the route of exposure.

• Animal model of SM was established by equal toxicity dose (1LD 50 )-induced acute pulmonary injury in rats using two methods. • Serum inflammatory factors and proteins in alveolar septa of the intraperitoneal SM group were increased. • The effects of SM may be related to its rapid absorption from the peritoneal cavity.

Objective: Sulfur mustard (SM) is a vesicant alkylating agent. There are still biochemical mechanisms underlying SM damage that are unknown. This study was to determine the differences of apoptosis and pulmonary fibrosis underlying SM-induced acute pulmonary injury via intraperitoneal injection and intratracheal instillation in rats. Methods: An acute pulmonary injury model was established in a preliminary experiment using intraperitoneal injection and intratracheal instillation of SM in rats, in order to determine the equal toxicity dose of SM (1LD50). Then, SM-induced changes in apoptosis and pulmonary fibrosis were observed by immunohistochemical staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Masson staining and electron microscopic observationin intraperitoneal and tracheal SM groups that were injected intraperitoneally and instilled intratracheally with diluted SM [0.1 mL per rat (0.98 LD50 = 2 mg/kg)] and SM [0.1 mL per rat (0.96 LD50 = 8 mg/kg)] respectively, and an untreated control group. Results: In the alveolar septum, the positive expression ratio of apoptotic cells, Bax, caspase-3, and caspase-9 by TUNEL and Immunohistochemistry (streptavidin-perosidase method) in the intraperitoneal SM group was increased compared with the tracheal SM group (P < 0.05), but a significantly lower positive expression ratio of Bcl-2 was detected (P < 0.05). Electron microscopic observations confirmed that the type I and II alveolar epithelial cells in lungs exhibited apoptotic morphologic features, such as cracked, lost, and disordered microvilli of membranes, fuzzy mitochondrial cristae, and detached, dissociated ribosomes from the surface of the rough endoplasmic reticulum. A significantly higher positive expression ratio of MMP-2, MMP-9, TIMP-1, TIMP-2, collagen type I, collagen type III, TGF-beta 1, and Smad7 by immunohistochemical staining in the alveolar septum were detected in the intraperitoneal SM group compared with the tracheal SM group (P < 0.05). Conclusions: These data demonstrated increased apoptosis and pulmonary fibrosis via intraperitoneal injection under equal toxicity doses SM (1LD(50)) in rats.

This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD50=8mg/kg) and SM (0.98 LD50=2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD50 doses.

Objective To establish rat model of sulfur mustard (SM)-induced acute lung injury via intraperitoneal and tracheal injection, in order to compare the differences of pulmonary fibrosis indexes. Methods A total of 136 male Sprague Dawley rats were randomly divided into the five groups, i.e. the control group with 8 rats and other four groups (intraperitoneal SM group, intraperitoneal propylene glycol group, tracheal SM group and tracheal propylene glycol group) with 32 rats in each group. The rats in the intraperitoneal SM group were intraperitoneally injected with 0.1 ml diluted SM (0.96 LD50 = 8 mg/kg), the rats in the tracheal SM group were intratracheally injected with 0.1 ml diluted SM (0.98 LD50=2 mg/kg), the rats in the intraperitoneal propylene glycol group and the tracheal propylene glycol group were injected with 0.1 ml propylene glycol through peritoneal cavity and trachea respectively; meanwhile the status quo was kept with the normal control group. SM-induced pulmonary fibrosis indexes were observed by Masson and immunohistochemical staining. Results Light microscopic observation confirmed that green-stained collagen fibers increased in the alveolar septa at 72nd h. Significantly higher positive expression rates of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemical staining in the alveolar septa were detected in the intraperitoneal SM groups compared with those in the tracheal SM groups at each period of time ( < 0.05). The positive expression rates of type Ⅰ collagen and type Ⅲ collagen in the alveolar septa in the intraperitoneal SM groups were significantly increased compared with those in the tracheal SM group at each period of time ( <0.05). Significantly higher positive expression rates of TGF-β1 and Smad7 in the alveolar septa were also observed in the intraperitoneal SM group compared with the tracheal SM group at each period of time ( < 0.05). Conclusions When LD50 concentration of SM through intraperitoneal injection is similar to that through tracheal injection in rat, the indexes of pulmonary fibrosis are significantly increased after intraperitoneal injection compared with those after tracheal injection, suggesting that SM-induced pulmonary fibrosis can be more easily induced through intraperitoneal injection.

Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent.

目的 经腹腔和气管建立大鼠芥子气(SM)肺损伤的动物模型,比较两种大鼠急性肺损伤模型炎性反应的差异.方法 选取Sprague Dawley大鼠136只,分为5组,正常对照组8只,其他4个组(腹腔SM组、腹腔丙二醇对照组、气管SM组、气管丙二醇对照组)每组32只.腹腔SM组腹腔内注入稀释的SM 0.1 mL(0.96 LD50＝8 mg/kg),气管SM组气管内注入稀释的SM 0.1 mL(0.98 LD50 =2 mg/kg),正常对照组不做任何处理.ELISA法检测支气管肺泡灌洗液和血液标本,HE染色和免疫组织化学判断炎性反应情况.结果 腹腔SM组各时间段支气管肺泡灌洗液蛋白含量和细胞计数与气管SM组相比显著升高(P＜0.05);腹腔SM组各时间段血清TNF-α、IL-1β、IL-6与气管SM组相比显著升高(P＜0.05);腹腔SM组各时间段肺泡间隔T、B淋巴细胞和巨噬细胞阳性表达率与气管SM组相比显著增加(P＜0.05).结论 大鼠在SM LD50相似的情况下,腹腔SM组支气管肺泡灌洗液、肺泡间隔及血清炎性反应指标明显高于气管SM组.

Objective To establish animal model of sulfur mustard (SM)-induced acute lung injury in rats via intraperitoneal and tracheal injection,in order to compare the difference of oxidative stress reaction.Methods 136 male Sprague Dawley rats were selected and randomly divided into five groups,the control group with eight cases,other four groups (i.e.the intraperitoneal SM group,the intraperitoneal propylene glycol group,the tracheal SM group,the tracheal propylene glycol group) with 32 cases in each group.The rats in intraperitoneal SM group were injected intraperitoneally with diluted SM 0.1 ml (0.96 LD50 =8 mg/kg),the rats in tracheal SM group were injected intratracheally with diluted SM 0.1 ml (0.98 LD50 =2 mg/kg),meanwhile the status quo was kept with the normal group.SM-induced oxidative stress was observed by enzyme linked immunosorbent assay and immunohistochemical staining.Results In bronchoalveolar lavage fluid,lactate dehydrogenase and glutathione peroxidase levels in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group (all P ＜0.05).Serum γ-glutamyl transpeptidase and thobarbituric acid reactive substances levels in the intraperitoneal SM group at a period of time were higher than those in the tracheal SM group (all P ＜0.05).In the alveolar septum,the positive expression ratios of 8-hydroxy deoxyguanosine,nuclear factorE2 related factor 2 and heme oxygenase-1 in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group (all P ＜0.05).Conclusions Under similar concentration of SM via intraperitoneal and tracheal injection in rats,indexes of lung oxidative stress in the intraperitoneal injection are increased compared with the tracheal injection,which may be related to fast absorption of the peritoneal cavity to SM.

目的 经腹腔和气管建立大鼠芥子气(SM)急性肺损伤动物模型,比较两种大鼠急性肺损伤模型细胞凋亡的差异.方法 选取Sprague Dawley大鼠136只,随机分为5组,正常对照组8只,其他4个组为腹腔SM组、腹腔丙二醇对照组、气管SM组、气管丙二醇对照组,每组32只.腹腔SM组腹腔内注入稀释的SM0.1 m1(0.96 LD50=8 mg/kg),气管SM组气管内注入稀释的SM 0.1 m1(0.98 LD50=2mg/kg),正常对照组未做任何处理.采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(TUNEL)染色和免疫组织化学法及电镜观察,判断细胞凋亡情况.结果 ①腹腔SM组各时间段肺泡间隔TUNEL染色阳性细胞表达率较气管SM组增多(P＜0.05).②腹腔SM组各时间段肺泡间隔凋亡蛋白Bax阳性表达率较气管SM组升高(P＜0.05);腹腔SM组各时间段肺泡间隔凋亡蛋白Bcl-2阳性表达率较气管SM组降低(P＜0.05).③腹腔SM组各时间段肺泡间隔凋亡蛋白酶Caspase-3、Caspase-9阳性表达率较气管SM组增多(P＜0.05).④电镜显示,染毒72h,腹腔SM组和气管SM组Ⅰ型和Ⅱ型肺泡上皮凋亡细胞形态特征为上皮细胞膜附着的微绒毛断裂缺失,排列紊乱;线粒体嵴模糊,粗面内质网表面附着的核糖体脱离,并游离于细胞质中.结论 SM经腹腔和气管染毒致大鼠急性肺损伤,通过内源性通道引发细胞凋亡调节异常,SM经腹腔染毒大鼠各项细胞凋亡指标比经气管明显升高,推测可能与SM腹膜腔的快速吸收有关.

AIMS:Hypoxia and high hydrostatic pressure can induce an increase in the thickness of the tunica media and intima; secondary vasa vasorum (VV) increase to fit the remodeling of the vessel wall. We aimed to investigate the impact of high hydrostatic pressure on VV in the varicose greater saphenous veins (VGSVs) and diseased splenic veins (DSVs).METHODS:We collected 34 VGSVs and DSVs. Thirty-four normal greater saphenous veins (GSVs) and splenic veins (SVs) were also collected (control group). Samples were cut into slices, and observed under both light and electron microscopy. The mean density and cross-sectional areas of the VV in the adventitia were measured.RESULTS:In both VGSVs and DSVs, VV density increased, in the adventitia and exterior tunica media, offering an intensive linear distribution. However, sporadic distribution of the interior tunica media and intima were seen on light microscopy. The integrated structure of the cell nucleus of endothelial cells in VV, normal morphology and distribution of chromatin, partially hyperchromatic mitochondria matrix, fuzzy or fractured mitochondria cristae, and medullary cristae changes were observed by electron microscopy. Mean density and cross-sectional areas of VV in the adventitia of GSVs and SVs were significantly different.CONCLUSION:Under high hydrostatic pressure conditions, the number of VV were increased in the wall of VGSVs and DSVs. There was heterogeneity between both types of veins. The splenic vein has a higher number of VV, but the greater saphenous vein has a higher average cross-sectional area. The same ultrastructural changes are seen in the endothelial cells of the VV in both vessels.

BACKGROUND:Following splenomegaly due to portal hypertension, pathologic characteristics include passive congestion and lymphoplasia. High venous pressure and hemodynamics can result in vascular proliferation and lymphoplasia, and promote splenic microcirculation and functional changes. The aim of this study was to determine the changes in penicillar arterioles (PAs) of red pulp in residual splenic tissue after subtotal splenectomy due to splenomegaly in cirrhotic patients to provide anatomic and physiologic evidence for reserved splenic surgery.METHODS:Thirteen patients with splenomegaly due to portal hypertension, who were treated surgically, comprised the splenomegaly group. After 8 years, we obtained another specimen by puncture biopsy from the residual spleen group. We designated patients with splenic trauma as the control group. The morphology of PAs under light microscopy was facilitated by EVG staining and immunohistochemistry for CD34. Semi-thin sections were HE-stained. The ultrastructure of PA endothelial cells was observed under electron microscopy.RESULTS:In the residual spleen group, diffuse distribution, tenuous elastic intima in the arterial wall, and continuity in PA of red pulp were seen under light microscopy. A significantly lower density and average cross-sectional area of PAs were observed in the residual spleen group compared with the splenomegaly and control groups (P < 0.01). A uniform mitochondrial matrix and a decreased number of ruptured cristae in PA endothelial cells were observed under electron microscopy. While there were some beneficial changes (splenic artery flow volume, portal venous diameter, and portal venous flow volume), the platelet and leucocyte counts were markedly increased in residual spleen.CONCLUSION:Subtotal splenectomy can eliminate the factors which precipitate splenomegaly (portal hypertension), improve the reconstruction of splenic capillaries, correct hypersplenism, and restore normal splenic function.

OBJECTIVE:To establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells.METHODS:One hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy.RESULTS:In the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeⅡalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05).CONCLUSION:The lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups.

Sulphur mustard (SM) is a corrosive alkylating agent that is likely to be absorbed in vivo through the lungs,eyes and skin into internal organs. SM not only can produce its peculiar cytotoxic?ity thought to be mediated by the alkylation of DNA,protein and nucleic acids,but is a strong mutagen and carcinogen. However,whatever the way SM poisoning occurs,lungs are the most vulnerable, and early death is mainly carused by both the acute respiratory distress syndrome and pulmonary infec?tion. In this review,we analyzed SM-induced lung injury mechanisms.

Objective To investigate the changes of penicillar arteriole (PA) of red pulp in residual splenic tissue after subtotal splenectomy due to portal hypertension in order to provide evidence for beneficial outcomes of reserved splenic surgery.Methods We analyzed 13 samples of splenic tissue following surgery for splenomegaly due to portal hypertension as our splenomegaly group.We then took biopsies from the spleens of the same 13 individuals after 8 years to analyze as our residual spleen group.Our control group consist of splenic tissue from 13 traumatic spleen patients.All tissues were then analyzed using EVG staining and immunohistochemistry to observe morphology of penicillar arteriole under light microscope.Results A significantly lower density of PA was observed in residual spleen group compared with splenomegaly group (7.63 ± 0.13 pieces/0.15 mm2 versus 9.53 ± 0.15 pieces/0.15 mm2,P ＜ 0.01),but higher compared with the control group (4.64 ± 0.15 pieces/0.15 mm2,P ＜ 0.01).Significantly lower average cross-sectional areas of penicillar arteriole was observed in residual spleen group compared with both the splenomegaly group (144.32 ± 16.53 μm2 versus (323.52 ± 99.31) μm2,P ＜ 0.01) and control group (185.0123.65 μm2,P ＜ 0.01).Conclusion Subtotal splenectomy attenuates initiation factors of splenomegaly due to portal hypertension,improves reconstruction of splenic capillaries,and promotes retension of immune function of the residual spleen.