目的 二甲双胍(metformin,Met)是临床常用的降血糖药,对能量代谢的调控是其药理作用主要机制之一.本文基于线粒体氧化呼吸链相关调控基因对二甲双胍的抗抑郁作用进行探索,以从能量代谢角度探讨其抗抑郁作用相关机制.方法 ICR小鼠皮下注射皮质酮(corticosterone,CORT,20 mg/kg)连续 3 周复制小鼠抑郁模型,注射一周后,二甲双胍(200、100、50 mg/kg)灌胃给药 2 周,给药期间测量小鼠糖水偏好率;给药结束后进行旷场试验,记录小鼠进入旷场中央区的次数和停留时间,在周边区域的跨格数;qPCR和Western blot检测海马组织中线粒体呼吸链相关基因Nduf(NADH dehydrogenase ubiquinone)和Mrp(mitochondrial ribosomal protein)mRNA表达,以及神经营养因子 BDNF(brain-derived neurotrophic factor)、环磷酸腺苷反应元件蛋白 CREB(cAMP response element-binding protein)和神经突触后受体AMPAR(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor)、NMDAR(N-methyl-d-aspartic acid receptor)mRNA或蛋白表达情况.此外,还观察了二甲双胍(连续灌胃给药 1 周)对正常小鼠的作用.结果 二甲双胍不影响正常和模型小鼠的体重;提高正常和模型小鼠的糖水偏好性;增加正常和模型小鼠进入旷场中央区域的次数,增加模型小鼠在外周区域的活动距离;二甲双胍上调正常和模型小鼠海马组织中Nduf、Mrp的大部分亚型的mRNA表达(除Ndufa8、Ndufa13);增强正常小鼠海马中Creb、Ampar、Nmdar mRNA表达和BDNF、CREB、AMPAR、NMDAR蛋白表达,拮抗模型小鼠中Bdnf、Creb mRNA和BDNF、CREB 蛋白表达的下调.结论 二甲双胍可以改善CORT所致小鼠抑郁样行为,其机制与调节海马组织中线粒体氧化呼吸链、神经可塑性相关的基因或蛋白表达有关.

Anemoside B4 (B4) is a saponin that is extracted from Pulsatilla chinensis (Bge.), and Regel exhibited anti-inflammatory, antioxidant, antiviral, and immunomodulatory activities. However, its hypoglycemic activity in diabetes mellitus has not been evaluated. Here, we explored the effect of B4 on hyperglycemia and studied its underlying mechanism of lowering blood glucose based on hyperglycemic rats in vivo and L6 skeletal muscle cells (L6) in vitro. The rats were fed a high-fat diet (HFD) for one month, combined with an intraperitoneal injection of 60 mg/kg streptozotocin (STZ) to construct the animal model, and the drug was administrated for two weeks. Blood glucose was detected and the proteins and mRNA were expressed. Our study showed that B4 significantly diminished fasting blood glucose (FBG) and improved glucose metabolism. In addition, B4 facilitated glucose utilization in L6 cells. B4 could enhance the expression of glucose transporter 4 (GLUT4) in rat skeletal muscle and L6 cells. Mechanistically, B4 elevated the inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Furthermore, we confirmed the effect of B4 on glucose uptake involved in the enhancement of GLUT4 expression in part due to PI3K/AKT signaling by using a small molecule inhibitor assay and constructing a GLUT4 promoter plasmid. Taken together, our study found that B4 ameliorates hyperglycemia through the PI3K/AKT pathway and promotes GLUT4 initiation, showing a new perspective of B4 as a potential agent against diabetes.

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.

一直以来对中医学与当代自然科学的关系存在着争论.对于中医学这种临床具有强大生命力的学科,从历史发展的角度对其进行分析定位,对于全面深入认识与发展中医学具有重要意义.为此,我们从西方自然哲学-自然科学的发展角度来探讨中医学的历史定位,从中获得对中医学的理性认识,为中医药学科的发展提供哲学和科学依据.结果表明:①从探讨自然运行规律来看,中医学属于科学范畴;②从历史角度来看,中医学应属于自然哲学下,与由数理实验科学发展而来的自然科学并列;③"形而上学-辨证论治-信息反馈修正"是其理论形成的主要闭环模式,并以此确保了这种形而上学与临床诊疗紧密结合在防治疾病上的可行性和可确证性;④对中医学的研究应该既不同于自然哲学也不同于自然科学;⑤坚持科学自觉和哲学自觉是研究发展中医学的重要治学态度.

目的 探讨常见急性肾损伤大鼠模型病理过程中其血清、尿蛋白的变化及其形成的相关机制.方法 分别尾静脉注射顺铂,腹腔注射庆大霉素,以及结扎肾动静脉所致肾缺血再灌(简称肾缺血再灌,renal ischemia reperfusion,RIR)等方法,造成大鼠急性肾损伤.观察肾组织形态学变化,检测血清和24 h尿总蛋白(total protein,TP),白蛋白(albumin,ALB)以及血清肝功肾功相关指标;观察肝脏组织TP,ALB的含量及ALB mRNA、蛋白的表达水平;观察肾组织ALB,肾病蛋白(Nephrin),足突蛋白(Podocin)及炎性坏死因子相关蛋白表达.结果 顺铂、肾缺血再灌及庆大霉素大鼠血清中ALB显著下降(P<0.05),同时尿ALB,TP显著升高(P<0.05).顺铂模型肝TP及ALB mRNA及蛋白表达下调,庆大霉素及肾缺血再灌模型肝TP含量显著升高(P<0.05),ALB mRNA表达上调.三种模型大鼠肾组织Nephrin,白介素-6(interleukin-6,IL-6),肿瘤坏死因子(tumor necrosis factor-α,TNFα),ALB蛋白表达均明显升高(P<0.05);顺铂及肾缺血再灌大鼠肾Podocin表达明显下调;同时3种模型大鼠肾组织均可见基底膜损伤,肾小管上皮细胞出现不同程度的坏死.结论 3种急性肾损伤大鼠尿蛋白排泄升高和血清ALB下降,与肾小球基底膜及肾小管上皮细胞损伤相关.同时肝脏和肾脏不同程度上启动了ALB表达合成.3种模型所致其病理生理变化不完全相同,因此在相关防治急性肾损伤中药研究中,还须对不同造模方法进行有针对性的观察.

目的 比较不同化疗药导致大鼠口腔溃疡的特点,寻找一种稳定可靠的化疗药导致的口腔溃疡模型.方法 大鼠右侧口腔黏膜内分别注射相应化疗药复制大鼠口腔溃疡模型,记录大鼠体质量、摄食量、溃疡直径;进行黏膜组织病理学观察,黏膜局部炎症因子等mRNA表达检测,脏器指数计算,外周血T淋巴细胞亚群检测.结果 造模后大鼠体质量、摄食量均明显下降;顺铂、紫杉醇组大鼠黏膜明显溃疡,组织病理学观察可见黏膜上皮受损脱落;黏膜组织IL-1βmRNA表达明显升高,EGFR mRNA表达明显降低,脏器指数无明显变化;甲氨蝶呤、长春新碱、阿霉素组无明显溃疡,但脏器指数下降,细胞因子表达下降;各组外周血T淋巴细胞亚群无明显差异.结论 大鼠口腔黏膜内局部注射化疗药顺铂或紫杉醇可形成稳定的口腔溃疡模型.溃疡直径、摄食量、细胞因子和炎症介质表达等可用于评价药物的治疗作用.

Colitis is not fully curable, although currently, some treatment options are being adopted. In this study, we investigated the effects of pineapple leaf phenols (PLPs), natural phenol products from pineapple leaves, on DSS-induced colitis in mice. The results showed that PLPs dramatically decreased the inflammatory response by inhibiting NF-κB activation and the secretion of pro-inflammatory factors. Moreover, PLPs provided protection against DSS-induced acute colitis by maintaining epithelial integrity. Caffeic and P-coumaric acids had similar effects and could be the active components responsible for PLPs' effect on colitis. These results indicate that the oral administration of PLPs might be considered as a therapeutic strategy in the treatment of patients with colitis. However, further research on clinical applications and the exact effect of PLPs on colitis is required.

目的 观察太子参多糖(总多糖)、葛根淫羊藿总黄酮(总黄酮)及其复合物对小鼠脑蛋白质组学的影响,探讨其神经细胞网络调控的潜在机理.方法 给正常小鼠分别灌胃太子参多糖(400 mg·kg-1)、葛根淫羊藿总黄酮(400 mg·kg-1)及其二者复合物(800 mg·kg-1),连续给药7天,第7天最后1次给药后1 h,处死动物,取脑.提取蛋白,利用LC/MS-MS测试蛋白表达的变化.通过DAVID数据库分析变化蛋白的功能及信号通路,STRING数据库分析变化蛋白的相互作用及其网络关系.结果 在所测试的5567个蛋白中,以上调蛋白占比较高,其中主要是线粒体的基因受到调控.总多糖、总黄酮及其复合物都上调的蛋白有8个,作用于线粒体的不同环节,提示该复合物抗抑郁作用的靶点主要在线粒体.太子参多糖的调控线粒体相关蛋白的作用揭示了其潜在的神经精神方面的药理作用.除此,还发现各有效部位调控蛋白的数量明显多于复合物,提示药物复合作用的复杂性.结论 总多糖、总黄酮及其复合物可以作用于脑神经元,并且主要以线粒体为主要靶点.该研究为相关中药调控神经精神功能活动提供了重要的蛋白线索及其实验依据.

Abstract Cisplatin (CP), an anticancer drug, often causes kidney damage. However, the mechanism of CP‐induced acute kidney injury (AKI) is not completely understood. AKI was induced by intravenous injection (i.v.) of cisplatin at doses of 5, 8, and 10 mg/kg. Anemoside B4 (B4) (20 mg/kg, i.m.) and dexamethasone (DXM) (0.5 mg/kg, i.v.) were used for AKI treatment. Biochemical indicators were assessed using an automatic biochemical analyzer, protein expression was analyzed by western blotting, and morphological changes in the kidney were examined by PAS staining. The serum creatinine (Cre) and blood urea nitrogen (BUN) levels did not change significantly in the first 2 days but abruptly increased on the third day after CP injection. The serum albumin (ALB) and total protein (TP) levels decreased in both a time‐ and dose‐dependent manner. The urine protein level increased, the clearing rate of Cre decreased distinctly, and morphologic changes appeared in a dose‐dependent manner. The protein expression of p53/caspase‐3, NLRP3, IL‐6, and TNF‐α was obviously upregulated on day 3; concurrently, nephrin and podocin were downregulated. The expression of LC3II and p62 was upregulated significantly as the CP dose increased. B4 and DXM obviously decreased the BUN and Cre levels after 3 or 5 days of treatment. AKI appeared distinctly in a time‐dependent manner at 2 to 5 days after the administration of 5 mg/kg CP and in a dose‐dependent manner upon the administration of 5, 8, and 10 mg/kg CP. The third day was a significant time point for renal deterioration, and treatment with B4 and DXM within the first 3 days provided significant protection against AKI.

Context Dexamethasone (DXM) has an anti-immunoinflammatory effect, and is often used in acute kidney injury (AKI). However, the effects of DXM on albumin (ALB) have not been fully studied. Objective To investigate the effects of DXM on ALB production and renal function. Materials and methods Male Wistar rats were divided into normal and DXM groups (0.25, 0.5, 1 mg/kg for 5 days) (n = 15) for a dose-dependent study. Rats were divided into normal group and DXM groups (0.5 mg/kg for 3, 5, 7 days) (n = 9) for a time-dependent study. In AKI experiment, rats were divided into normal (saline), cisplatin (CP, 5 mg/kg, i.v.), CP + DXM groups (0.25, 0.5 and 1 mg/kg, i.m.) (n = 16). The blood and the organs were isolated for analysis. Results In normal, serum ALB (sALB) and serum total protein (sTP) increased in DXM group with sALB increased 19.8-32.2% (from small to large dosages); and 30.2-32.5.6% (from 3 to 7 days of DXM); sTP 15.7-22.6% and 14.2-24.3%; urine ALB (uALB) 31.5-392.3%, and 1047.2-1390.8%; urine TP (uTP) 0.68-173.1% and 98.0-504.9%, compared with normal groups. DXM increased the mRNA expression of Cebp and Hnf, suppressing podocin. In AKI, DXM decreased serum BUN (53.7%), serum Cre (73.4%), sALB (30.0%), sTP (18.7%), uALB (74.5%), uTP (449.3%), rescuing the suppressed podocin in kidney. Conclusions DXM acts on Cebp and Hnf and promotes ALB production. This finding helps to evaluate the rationale of DXM for kidney injury.

This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1β, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.

Objective: To investigate the protective effect of Pulsatilla saponin B4 on acute renal injury and acute toxicity in mice. Methods: In vitro, the cell experiments were performed to induce HEK293 injury model by LPS, and B4 was used for 24 and 48 hours. MTT assay was used to detect the activity of cells and the expression of inflammatory factors by q PCR to observe the effect of B4 on renal cell injury. The animal experiments were conducted in rats and mice. In pharmacological study, rats or mice were given glycerol, cisplatin, and lipopolysaccharide (LPS) respectively for acute renal injury. B4 was injected into the caudal vein at different doses. After given for a certain period of time, orbital blood was collected and the serum was separated. Serum BUN, creatinine (Cre), total protein (TP) and rat's urinary protein in rats were determined to evaluate the effect of B4 on the renal damage. In the acute toxicity, mice were injected intravenously with different doses of B4 for2 weeks. According to the death, the half-lethal dose (LD50) was calculated. Results: B4 could increase the activity of injured renal cells and down-regulate the expression of inflammatory factor TNF-α. It also inhibit the increase of serum BUN, Cre induced by cisplatin and LPS caused by increased significantly. At the same time, B4 with high dose (2. 5 mg·kg-1) could also significantly reduce rat urine protein concentration. Its effective dose were 1. 25-2. 5 mg·kg-1in rats, and 5-10 mg·kg-1in mice. The LD50 for intravenous administration of B4 to mice was 3. 36 g·kg-1and the 95％ confidence limit was 3. 34 to 3. 37 g·kg-1. And therefore, the clinical safety index of B4 was 168 (3. 36/0. 02) based on the maximum dose of 20 mg·kg-1in mice, showing B4 has a high clinical safety range. Conclusion: B4 has definite protective effect on experimental acute renal impairment, and meanwhile its large clinical safety index suggests that this compound has a good prospects for the development of new drugs.

Dihydrotanshinone (DHT), one of the major ingredients of Salvia miltiorrhiza Bunge (Danshen), displays many bioactivities. However, the activity and underlying mechanism of DHT in anti-inflammation have not yet been elucidated. In this study, we investigated the anti-inflammatory activity and molecular mechanism of action of DHT both in vitro and in vivo. Our data showed that DHT significantly decreased the release of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, THP-1 cells, and bone marrow-derived macrophages (BMDMs), and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, flow cytometry results indicated that DHT reduced the calcium influx, and generation of reactive oxygen species (ROS), and nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells. Moreover, DHT suppressed the transcription of nuclear factor-κB (NF-κB), the expressions of NF-κB proteins, and nuclear translocation of NF-κB/p65, thereby suggesting that the NF-κB pathway played a role in the anti-inflammatory action of DHT. In addition, DHT attenuated LPS-challenged activator protein-1 (AP-1) activity, resulting from interference of the mitogen-activated protein kinase (MAPK) pathway. The molecular docking simulation of DHT to toll-like receptor 4 (TLR4) suggested that DHT binds to the active sites of TLR4 to block TLR4 dimerization, which was further corroborated by cellular thermal shift assay and co-immunoprecipitation (Co-IP) experiments. Furthermore, the recruitment of myeloid differentiation primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization. Thus, investigating the molecular mechanism of DHT indicated that TLR4-MyD88-NF-κB/MAPK signaling cascades were involved in the anti-inflammatory activity of DHT in vitro. In in vivo mouse models, DHT significantly ameliorated LPS-challenged acute kidney injury, inhibited dimethylbenzene-induced mouse ear oedema, and rescued LPS-induced sepsis in mice. Taken together, our results indicated that DHT exhibited significant anti-inflammatory activity both in vitro and in vivo, suggesting that DHT may be a potential therapeutic agent for inflammatory diseases.

Context: Lipopolysaccharide (LPS) is often used to induce immunoinflammatory reactions. TLR4/NFκB and NLRP3 signalling are major factors for inflammation. Dexamethasone (DXM) has an anti-immunoinflammatory effect. Objective: To investigate the inflammatory reaction in pathological changes of organs and the expression of inflammatory signalling during LPS infection. Materials and methods: ICR mice were divided into control group (n = 9), LPS group (n = 15) and LPS + DXM group (n = 14). LPS (10 mg/kg) was injected intravenously in LPS group and LPS + DXM group, normal saline was injected to the control group; DXM (0.5 mg/kg) was given by intragastric administration. 12 h after LPS, the blood was collected and the organs were isolated for biochemical analysis, protein expression, and morphological examination. Results: The results showed that BUN, Cre, ALT, AST in the LPS group increased distinctly by 81.42, 67.84, 40.53 and 36.05%, respectively, and CK, ALP, TP and ALB decreased by 71.37, 60.6, 12.57 and 19.73%, respectively, compared with the control group. In the morphologic observation, local necrosis in the liver, arterial vasodilation in the heart and kidney, alveolar secretions and pulmonary interstitial in the lungs, and mucosal shedding in the small and large intestines, the expression of TLR4-NFκB signalling were up-regulated distinctly whereas NLRP3 signalling was less broadly affected. DXM can decrease BUN and Cre, downregulate the expression of TLR4-NFκB signalling, but has no effect on the organ damage based on morphology. Conclusion: Acute injuries induced by LPS are extensive. The inflammatory damage in small and large intestines, liver and kidney was more severe than other organs. TLR4-NFκB signalling was the major response to LPS stress.

目的:观察比较内毒素(LPS)、甘油、顺铂和庆大霉素等4种因素所致实验性急性肾损伤动物血清尿素氮(BUN)和肌酐(Cre),以及肾脏相关炎性坏死因子表达的变化.方法:采用大、小鼠进行整体动物实验.给小鼠腹腔注射顺铂或尾静脉注射LPS,给大鼠肌肉注射甘油或腹腔注射庆大霉素,造模一定时间后行眼眶静脉采血,分离血清,测试血清BUN、Cre.以qPCR法检测白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、白细胞介素6 (IL-6)、转录因子κB (NF-κB)、凋亡坏死因子(Caspase3)、模式识别受体TLR4等mRNA表达.结果:LPS、甘油、顺铂和庆大霉素均可导致血清BUN、Cre升高.四种因素所致急性肾损伤中,肾小管均出现不同程度的损伤.LPS所致肾组织损伤可见白细胞浸润,甘油、顺铂和庆大霉素肾损伤动物肾小管内出现蛋白管型.此外炎性坏死因子表达明显升高,除顺铂组大鼠肾脏凋亡坏死因子Caspase3表达明显升高外,其它三种因素所致肾脏的Caspase3未见明显变化.地塞米松可以明显降低血清BUN和Cre,下调炎性坏死因子及凋亡因子的表达.结论:四种因素可以明显致实验性急性肾损伤,同时使受损肾脏炎性坏死子mRNA表达明显升高,与血清BUN和Cre的升高具有相关性.除此,顺铂还伴有凋亡因子Caspase3表达的明显上调,表现出与其它三种因素的不同性.地塞米松对于实验性急性动物肾功能损伤具有明确的保护作用.

Anemoside B4 (B4) isolated from Radix Pulsatilla has anti-inflammatory activities in the colon and antitumor effects. However, its role in the prevention and treatment of kidney injury has not been reported. Here, we reported the effects of B4 on chronic kidney injury (CKI) and studied its related mechanism based on an adenine-induced kidney injury model in rats. The results showed that serum BUN (blood urea nitrogen), Crea (creatinine), and urinary proteins increased significantly after oral administration of adenine. Meanwhile, the adenine contents in both renal tissue and urine increased markedly compared with those of normal rats. Moreover, IL-1β, IL-6, TNFα, and NFκB expression was upregulated in the kidney. Simultaneously, the expression of NLRP3 (the nucleotide-binding and oligomerization domain–like receptor, leucine-rich repeat and pyrin domain–containing 3) in the inflammasome, which consists of Caspase 1, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and IL-18, was significantly upregulated. B4 could significantly decrease BUN and Crea; reduce urinary proteins in rats; suppress the expression of IL-6, IL-1β, NFκB, NLRP3, Caspase 1, ASC, and IL-18; and increase urinary adenine contents and promote its excretion. In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.