Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder linked to oxidative stress, mitochondrial damage, and impaired mitophagy. Tanreqing (TRQ) inhalation solution is widely used for respiratory diseases but its mechanism against COPD remains poorly defined. Here we investigated the protective effects of TRQ and its underlying pathway in a COPD rat model and cigarette smoke extract (CSE)-stimulated A549 cells. Our results showed that TRQ treatment alleviated body weight loss, lung pathological injury, alveolar destruction, and airway remodeling in rats. TRQ reduced ROS and MDA levels, restored SOD activity, and improved mitochondrial function including ATP production, mitochondrial membrane potential, and mitochondrial permeability transition pore homeostasis. Moreover, TRQ enhanced autophagy and mitophagy by upregulating Bnip3, Nix, Pink1, and Parkin expression. In vitro, knockdown of Pink1 abolished TRQ-mediated mitophagy activation, confirming that the Pink1/Parkin pathway was essential for TRQ action. In conclusion, TRQ inhalation solution ameliorates COPD by suppressing oxidative stress and restoring mitochondrial homeostasis via activating Pink1/Parkin-mediated mitophagy. This study identifies TRQ as a promising candidate for COPD treatment.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.

Chronic obstructive pulmonary disease(COPD)is a heterogeneous disease with a complex pathogenesis,which causes the lack of pre-cise and personalized prevention,control,and treatment approaches in clinical practice.Traditional Chinese medicine(TCM)with mul-tiple components acting on multiple targets plays a role in the prevention and treatment of COPD.After evaluating the treatment of cough,dyspnea,and lung distension based on syndrome differentiation in TCM,we summarized the commonly used TCM preparations for treating COPD.These preparations are mainly composed of medicines for clearing interior heat and releasing exterior,tonifying,ac-tivating blood and resolving stasis,resolving phlegm,relieving cough and breathlessness,and regulating Qi movement.Because all of them contain a variety of active ingredients such as flavonoids,terpenoids,and phenols,we analyzed the mechanisms of the classic prescriptions alone or in combination with other medicines or therapeutic methods.These mechanisms involve counteracting inflamma-tion,oxidative stress,and fibrosis,inhibiting apoptosis,alleviating airway remodeling,and enhancing immunity.Meantime,we summa-rized the existing problems in the treatment of COPD by TCM.This review provides a scientific basis for the research and treatment of COPD in the future.

Background: Luteolin-7-O-glucuronide (L7Gn) is a flavonoid isolated from numerous traditional Chinese herbal medicines that exerts anti-inflammatory effects. Previous research has revealed that aerosol inhalation is the most straightforward way of administration for the delivery of respiratory agents. Thus far, the impact of aerosol inhalation of L7Gn on lung inflammation and the underlying mechanisms remain unknown. Methods: The real-time particle size for L7Gn aerosol inhalation was detected by the Spraytec spray droplet size measurement system, including transmission and size diameters. The acute lung injury (ALI) rat model was induced by aerosol inhalation of LPS to evaluate the protective effect of L7Gn. The inhibitory effect of NLRP3 inflammasome activation assays was conducted in LPS-induced MH-S cells. Elisa, Western blotting, and RT-PCR were utilized to investigate the expression of NLRP3 inflammasome-relevant proteins and genes. Results: In this study, we found that inhalation of L7Gn aerosol significantly reduced pulmonary injury by inhibiting inflammatory infiltration and enhancing lung function. Meanwhile, the NLR family pyrin domain containing 3 (NLRP3) inflammasome was activated dramatically, accompanied by upregulated expression of IL-1β and IL-18, both in the ALI rat model and in LPS-induced MH-S cells. Moreover, L7Gn was found to significantly downregulate the expression of NLRP3, ASC, caspase-1, and cleaved caspase-1, which are critical components of the NLRP3 inflammasome, as well as the expression of IL-1β and IL-18. Conclusions: Based on our findings, L7Gn could exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation, which may emerge as potential therapeutic agents for the treatment of ALI.

目的 基于醒脑静雾化吸入给药粒径分布,多次雾化吸入给药黏膜过敏及刺激性,观察醒脑静雾化吸入给药的解热作用,为醒脑静临床雾化吸入给药提供依据和基础.方法 采用激光衍射法检测醒脑静雾化产生的粒径;通过连续多次雾化吸入给药观察醒脑静雾化吸入给药对大鼠黏膜刺激性;通过豚鼠全身主动过敏实验考察醒脑静雾化吸入给药过敏反应;采用干酵母致热模型观察醒脑静雾化吸入溶液解热作用.结果 粒径分布结果显示,醒脑静雾化最小粒径为0.117μm,90％粒径在10 μm以下左右,Dv(50)=4.76 μm提示醒脑静雾化后能够进入各级支气管及肺.刺激实验结果显示醒脑静雾化给药对大鼠肺灌洗液白细胞及其分类无显著影响,病理结果显示对鼻黏膜、咽喉、气管和肺部无明显影响.过敏结果显示醒脑静雾化吸入给药豚鼠全身主动过敏反应阴性.解热实验结果表明,醒脑静吸入给药能够明显抑制干酵母诱导发热模型大鼠的体温升高,能够降低下丘脑前列腺素E2(prostaglandin E2,PGE2)及环磷酸腺苷(cyclic adeno-sine monophosphate,cAMP)的含量和血清中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的含量.结论 醒脑静雾化粒径能够进入各级支气管及肺,雾化吸入后对大鼠粘膜无刺激性,豚鼠全身主动过敏反应阴性.对干酵母诱导的大鼠发热模型具有解热作用,其作用机理可能与其降低下丘脑PGE2及cAMP和血清中TNF-α的含量有关.

Purpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification.Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis.Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-kappa B signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-kappa B pathway including IL-17A, IL-17RA, NF-kappa B p65, C-X-C motif ligand 2, MMP1 and MMP13. Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-kappa B pathway.

目的:制备咖啡酸分子烙印聚合物(MIP)并特异性地去除金银花提取物中的咖啡酸,考察咖啡酸去除前后金银花提取物抑制前列腺素E2(PGE2)释放的变化,从整体上评价其抗炎活性.方法:采用溶胶-凝胶法,以粒径为 62～105 μm的二氧化硅微珠为载体、咖啡酸为模板分子、(3-氨丙基)三乙氧基硅烷为功能单体、四乙氧基硅烷为交联剂、四氢呋喃为溶剂,合成了咖啡酸MIP.以此MIP作为液相色谱固定相,以甲醇-乙酸(500∶1和 9∶1)为流动相,特异性去除了金银花提取物中的咖啡酸.通过脂多糖刺激巨噬细胞RAW264.7 释放PGE2 实验评价去除咖啡酸前后金银花提取物的抗炎作用.结果:溶胶-凝胶法制备的咖啡酸MIP能够从复杂体系中特异性地分离和富集微量的咖啡酸,对咖啡酸的容量因子和烙印效率分别为 15.8 和 9.7,最终从金银花提取物 2.6 g中分离了咖啡酸146 μg,纯度为 92%,回收率为 89%.金银花提取物和去除咖啡酸的提取物在质量浓度为 100、200、400 μg·mL-1时对脂多糖诱导的RAW264.7 细胞释放PGE2 的抑制率分别为 5.8%、35.6%、62.5%和 5.4%、13.3%、57.5%,去除微量咖啡酸以后的提取物在 3 个质量浓度时的抑制率较金银花提取物均有所降低.结论:咖啡酸是金银花提取物抗炎活性的一个重要成分,咖啡酸分子烙印聚合物可以实现金银花提取物中微量咖啡酸的特异性分离,分子烙印技术能够在保证中药完整性的前提下评价中药的药理活性.

Shiwei Longdanhua Granule (SWLDH) is a classic Tibetan medicine (TM) ranking in the top 20 Chinese patent medicines in prescription rate to treat respiratory diseases like pneumonia, acute and chronic tracheobronchitis, acute exacerbation of COPD and bronchial asthma in solution of inflammation, cough and phlegm obstruction in clinical practice. However, its systematic pharmacological mechanisms have not been elucidated yet. Here, we studied the therapeutic efficacy of SWLDH in treatment of acute respiratory diseases in BALB/c mice by comprehensive analysis of airway inflammation, oxidative stress, mucus hypersecretion, cough hypersensitivities and indicators associated with the development of chronic diseases. Our results show that SWLDH might exhibit its inhibitory effects on pulmonary inflammation by interference with arachidonic acid (AA) metabolism pathways. Oxidative stress that highly related to the degree of tissue injury could be alleviated by enhancing the reductive activities of glutathione redox system, thioredoxin system and the catalytic activities of catalase and superoxide dismutase (SOD) after SWLDH treatment. In addition, SWLDH could significantly abrogate the mucus hypersecretion induced bronchiole obstruction by inactivate the globlet cells and decrease the secretion of gel-forming mucins (MUC5AC and MUC5B) under pathological condition, demonstrating its mucoactive potency. SWLDH also showed reversed effects on the release of neuropeptides that are responsible for airway sensory hypersensitivity. Simultaneously observed inhibition of calcium influx, reduction in in vivo biosynthesis of acetylcholine and the recovery of the content of cyclic adenosine monophosphate (cAMP) might collaboratively contribute to cause airway smooth muscle cells (ASMCs) relexation. These findings indicated that SWLDH might exhibited antitussive potency via suppression of the urge to cough and ASMCs contraction. Moreover, SWLDH might affect airway remodeling. We found SWLDH could retard the elevation of TGF-β1 and α-SMA, which are important indicators for hyperplasia and contraction during the progression of the chronic airway inflammatory diseases like COPD and asthma.

目的 基于细胞色素P450(CYP450)系统研究乌头碱配伍鞣花酸、甘草苷减毒机制.方法 将HepG2细胞分为空白组、乌头碱组、鞣花酸组、甘草苷组、乌头碱+鞣花酸组、乌头碱+甘草苷组、乌头碱+鞣花酸+甘草苷组,CCK8法和LDH法分别检测细胞活力和细胞毒性,高内涵分析技术检测细胞数目、DNA和活性氧(ROS)含量及线粒体膜电位(MMP),RT-PCR和Western blot检测CYP1A2、CYP2C9和CYP3A4 mRNA及蛋白表达.结果 与空白组比较,乌头碱组细胞ROS含量显著增加,MMP显著降低(P<0.05),乌头碱+鞣花酸+甘草苷组细胞ROS、MMP差异无统计学意义(P>0.05).RT-PCR和Western blot结果显示,与空白组比较,乌头碱组细胞CYP1A2、CYP3A4 mRNA和蛋白表达显著降低(P<0.05),甘草苷组细胞CYP1A2、CYP2C9、CYP3A4 mRNA和蛋白表达显著升高(P<0.01,P<0.05);与乌头碱组比较,乌头碱+鞣花酸+甘草苷组细胞CYP1A2、CYP3A4 mRNA和蛋白表达显著升高(P<0.01,P<0.05,P<0.001).结论 乌头碱配伍鞣花酸、甘草苷可上调CYP1A2、CYP3A4表达,减少乌头碱在体内蓄积时间,起到减毒作用.

[目的]研究香砂平胃颗粒对正常小鼠及胃肠动力障碍模型小鼠胃排空、肠推进和血清中胃动素(MOT)、胃泌素(GAS)、生长抑素(SS)、P物质(SP)和生长激素释放肽(Ghrelin)含量的影响.[方法]灌胃给予正常小鼠及阿托品所致胃肠动力障碍模型小鼠香砂平胃颗粒高、中、低剂量(2.6 g/kg、1.3 g/kg、0.65 g/kg),采用称重法计算小鼠胃残留率和小肠炭末推进法计算小鼠肠推进率,进一步应用ELISA方法检测小鼠血清中MOT、GAS、SS、SP及Ghrelin的含量,并利用RT-PCR技术检测下丘脑中Ghrelin mRNA与生长激素促分泌素受体(GHSR)mRNA转录水平.[结果]在胃肠运动方面,香砂平胃颗粒高剂量组能显著促进正常小鼠的胃排空(P<0.05),并能拮抗阿托品所致小鼠的胃排空抑制作用(P<0.05),香砂平胃颗粒高、中、低剂量组均能显著拮抗胃肠动力障碍模型小鼠的小肠推进抑制作用(P<0.05或P<0.01);在胃肠激素方面,香砂平胃颗粒高剂量组能提高正常小鼠及胃肠动力障碍模型小鼠血清中MOT和GAS水平(P<0.05或P<0.01),且能上调胃肠动力障碍模型小鼠血清中Ghrelin含量与下丘脑中Ghrelin mRNA转录水平(P<0.01).[结论]香砂平胃颗粒能提高正常小鼠与胃肠动力障碍模型小鼠的胃肠动力,其作用机制可能与增加血清中MOT、GAS与Ghrelin含量有关.

Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.

Objective To study the therapeutic effect of Tanreqing Injection(痰热清注射液)on chronic obstructive pulmonary disease(COPD)model rats,and explore its possible mechanism by tandem mass tags(TMT)quantitative protein omics.Methods Wistar rats were randomly divided into control group,model group,dexamethasone(4 mg/kg)group and Tanreqing Injection high-,medium-and low-dose(4,2,1 g/kg)groups.Except for the control group,COPD models were prepared in other groups,and the corresponding drugs were given to each group.After 90 d of continuous administration,lung function and cytokine level in alveolar lavage fluid were detected.Hematoxylin-eosin and picrosirius red staining were used to observe the pathological changes of lung tissue.The differential proteins in lung tissue of rats in control group,model group and Tanreqing Injection medium-dose group were analyzed by TMT quantitative protein omics.Results Compared with control group,the autonomic activity and mental state of rats in model group were decreased,the compliance of lung function was decreased(P＜0.001),the resistance was increased(P＜0.001),inflammatory cells infiltrated in lung tissue,alveolar cavity expanded and collagen fibers deposited in airway wall,which indicated that the COPD model was successfully prepared.Compared with model group,the lung function of rats in Tanreqing Injection group was significantly improved(P＜0.01,0.001),and the levels of inflammatory factors in alveolar lavage fluid were significantly decreased(P＜0.05,0.01,0.001).Proteomic analysis showed that there were 61 differential proteins in Tanreqing Injection medium-dose group and model group,which were closely related to cell necrosis,apoptosis,autophagy and other signal pathways.Conclusion Tanreqing Injection can obviously improve the lung function and other symptoms of COPD model rats,and its mechanism is closely related to signal pathways such as cell necrosis,apoptosis and autophagy.

Tibetan medicine is one of the oldest traditional medicine systems in the world. Taking the Ruyi Zhenbao tablet (RYZB) as an example, which is a widely used classic oral Tibetan medicine, this article discusses the pharmacokinetics of single administration and long-term treatment and analyzed its metabolic properties and tissue distribution in vivo. After single administration, blood samples were collected before administration and at different time points after administration in different groups of rats. In the study of long-term treatment effects, blood samples were collected from the animals in each group on days 1, 15, and 30 and on day 15 after withdrawal. The results showed that after a single administration, the dose change had no significant effect on the T1/2 and Tmax of agarotetrol, isoliquiritigenin, and piperine (p > 0.05). There was a certain correlation between the increase in AUC0-t and the Cmax of agarotetrol, isoliquiritigenin, piperine, and the increase in dosage, with a dose range of 0.225–0.900 g/kg. There were no significant differences in Cmax and AUC0-t of ferulic acid at different doses (p > 0.05). Meanwhile, there was no significant sex-based difference in the pharmacokinetic parameters of these four components in rats. After long-term administration, the distribution agarotetrol in various tissues of rats was kidney > liver > heart > brain; the tissue distribution in low- and medium-dose groups of isoliquiritigenin was liver > kidney > heart > brain, and in the high-dose group, kidney > liver > heart > brain. The tissue distribution of piperine in each dose group was liver > kidney > heart > brain, and that of ferulic acid in each dose group was kidney > liver > heart > brain. Through the establishment of the previously developed methodology, the pharmacokinetic properties of RYZB were analyzed after a single administration and long-term administration. Our findings confirmed this approach for the exploration and establishment of a pharmacokinetic evaluation of Tibetan medicine, to support its guiding role in clinical application, but also to accelerate research into Tibetan medicine theory and medicine and to provide a solid foundation for the translation of Tibetan medicine throughout the world.

目的:探讨复方苦参注射液与血必净注射液对大鼠急性肺损伤的作用.方法:将Wistar大鼠随机分为正常组、模型组、阳性对照(地塞米松注射液)组、血必净注射液组及苦参高、中、低剂量组.除正常组外,其余各组均采用脂多糖(LPS)建立急性肺损伤大鼠模型,连续3d.造模后立即给药,末次造模后15 h给予第4次给药.给药后1h处死动物,取肺灌洗液和肺组织,采用酶联免疫吸附试验(ELISA)法检测肺灌洗液和组织匀浆中白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子(TNF-α)和核因子(NF)-κB的含量,苏木精—伊红(HE)染色观察肺组织病理学变化.结果:与正常组比较,模型组肺组织炎性细胞浸润程度升高,阳性对照组、血必净注射液组、苦参高剂量组肺组织炎性细胞浸润程度低于模型组.与模型组比较,苦参高、中剂量组和血必净注射液组肺灌洗液和肺组织中IL-1β、IL-6、NF-κB和TNF-α水平降低(均P＜0.05);与血必净注射组比较,苦参注射液中剂量组肺灌洗液和肺组织中NF-κB、TNF-α水平降低(P＜0.05).结论:复方苦参注射液和血必净注射液在治疗急性肺损伤方面均有一定的效果,能够有效抑制炎症反应,且前者的效果更为明显.

目的 探讨复方苦参注射液对博来霉素诱导肺纤维化模型大鼠的影响及相关机制.方法 将120只SD大鼠随机分为对照组、假手术组、模型组及复方苦参注射液低、中、高剂量(注射液原液l、2、4 mL·kg-1)组,每组20只,采用气管内注射博来霉素方法制备肺纤维化大鼠模型,造模24 h后给药组ip复方苦参注射液,第14、28天取材.观察大鼠一般状态、肺系数、肺功能、肺组织病理变化,并采用酶联免疫吸附法(ELISA)检测大鼠血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β (IL-1β)的水平,进一步检测肺组织中羟脯氨酸(HYP)、丙二醛(MDA)和超氧化物歧化酶(SOD)表达量的变化.结果 大鼠的一般情况观察发现,与假手术组比较,模型组大鼠食量及饮水量均有所下降,精神萎靡,毛色暗淡发黄,同时模型组大鼠出现拱背及口唇、爪甲及尾尖均呈现紫黯现象,部分大鼠出现口鼻出血,呼吸困难现象.给予复方苦参注射液后,肺纤维化模型大鼠的活动和精神状态均有改善作用.与假手术组比较,模型组大鼠体质量明显降低(P＜0.01、0.001),肺系数显著增加(P＜0.001),肺功能指标潮气量下降(P＜0.001),气道阻力升高(P＜0.001),动态肺顺应性降低(P＜0.001),肺组织发生纤维化、炎细胞浸润等明显损伤,血清中TNF-αt和IL-1β水平显著升高(P＜0.001),肺组织中HYP水平显著升高(P＜0.001),而SOD活性则显著下降(P＜0.001),MDA水平有增加趋势.与模型组比较,复方苦参注射液低、中剂量组大鼠体质量显著增加(P＜0.05、0.001),大鼠肺系数显著降低(P＜0.05、0.001),潮气量显著上调(P＜0.001),气道阻力显著降低(P＜0.01、0.001),动态肺顺应性显著上调(P＜0.01、0.001),大鼠肺组织纤维化程度明显减轻,血清中TNF-α水平降低(P＜0.01、0.001),肺组织中HYP含量显著降低(P＜0.01),SOD活性则显著升高(P＜0.05、0.01、0.001),MDA有下调趋势,但差异不显著.结论 复方苦参注射液可改善肺纤维化模型大鼠肺功能与肺部形态学病变,降低血清中TNF-α水平,以及下调肺组织中HYP含量与提高SOD活性,减轻炎性反应并增加抗氧化能力,对肺纤维化大鼠产生保护作用.

目的 探讨参苓健脾胃颗粒对脾虚模型大鼠的胃肠调节作用及机制.方法 将60只大鼠随机分为对照组、模型组、莫沙必利(1.35 mg·kg-1)组和参苓健脾胃颗粒低、中、高剂量(0.45、0.90、1.80 g·kg-1)组,每组10只.对照组在正常实验环境中饲养,给予正常饲料;其余各组均按照25 mL·kg-1于实验1、3、5、7、9、11、13dig给予液体猪油,并于2、4、6、8、10、12、14dig给予25 mL·kg-1 30％蜂蜜水;同时每天将大鼠放入水深约20 cm,水温为25～29℃的桶中进行20 min游泳,随后将大鼠饲养于含有浸湿刨花垫料的饲养笼中,造模时间为14 d.从第15天开始,将大鼠置于正常环境中饲养,并开始ig给予药物,每天1次,连续14 d.采用称质量法计算大鼠胃残留率,小肠炭末推进法计算大鼠肠推进率;采用间苯三酚法检测大鼠尿D-木糖排泄率;利用酶联免疫吸附法检测大鼠血清胃动素(MTL)、胃泌素(GAS)、生长抑素(SS)和P-物质(SP)水平,以及炎性因子白细胞介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)水平;利用实时荧光定量PCR(qRT-PCR)法检测大鼠结肠黏膜水通道蛋白3(AQP3)mRNA转录水平的变化.结果 实验期间,对照组未见异常,模型组出现厌食、倦怠、迟钝、便溏等现象,体质量增长减缓,从第13天开始,体质量显著低于对照组(P＜0.00l);给药结束,参苓健脾胃颗粒大鼠状态明显改善,实验25、28d,与模型组比较,参苓健脾胃颗粒中、高剂量组大鼠体质量显著增加(P＜0.001).与模型组比较,参苓健脾胃颗粒中、高剂量组胃排空率增加(P＜0.001),参苓健脾胃颗粒低、中和高剂量组小肠炭末推进率显著增加(P＜0.01、0.001);参苓健脾胃颗粒中、高剂量组尿D-木糖排泄率显著增加(P＜0.05);参苓健脾胃颗粒中、高剂量组MTL水平显著升高(P＜0.05、0.001),参苓健脾胃颗粒低、中和高剂量组GAS水平显著升高(P＜0.05、0.001),参苓健脾胃颗粒高剂量组SS水平显著降低(P＜0.01);参苓健脾胃颗粒高剂量组血清TNF-α水平显著降低(P＜0.01),参苓健脾胃颗粒中、高剂量组IL-10含量显著增高(P＜0.01、0.001);参苓健脾胃颗粒高剂量组AQP-3 mRNA转录水平显著上调(P＜0.05).结论 参苓健脾胃颗粒治疗脾虚模型大鼠的作用机制可能与其增强胃肠运动、增加胃肠激素分泌、抑制湿阻所致的消化道炎症以及促进水分从肠腔的吸收有关.

[目的]探讨龟苓膏对甲状腺功能亢进引发的阴虚火旺模型大鼠第二信使、能量代谢及氧化应激的影响.[方法]将50只SD大鼠随机分为空白组、模型组和龟苓膏低、中、高剂量组,每组10只.龟苓膏低、中、高剂量组(剂量分别为3.4 g生药/kg、6.8 g生药/kg、13.6 g生药/kg)预给药7 d,第8 d起模型组和龟苓膏低、中、高剂量组每天上午灌胃150 mg/kg优甲乐混悬液制备阴虚火旺模型大鼠,90 min后灌胃给予低、中和高剂量的龟苓膏,连续14 d,期间观察大鼠一般状态,检测大鼠环磷酸腺苷(cAMP)含量、环磷酸鸟苷(cGMP)含量、Na+-K+-ATP酶活性、Ca2+-Mg2+-ATP酶活性,以及超氧化物歧化酶(SOD)活性、丙二醛(MDA)和皮质醇(Cor)的含量.[结果]与模型组比较,龟苓膏各剂量组大鼠的烦躁情况改善,高剂量组大鼠体质量增加(P<0.01);龟苓膏中、高剂量组cAMP/cGMP比值显著降低(P<0.01);龟苓膏低、中、高剂量组Na+-K+-ATP酶活性显著降低,SOD活性显著提高(P<0.05或P<0.01);龟苓膏中、高剂量组MDA的含量显著降低(P<0.05或P<0.01).[结论]龟苓膏对甲状腺功能亢进引发的阴虚火旺所致的cAMP/cGMP比值增加、Na+-K+-ATP酶活性增强、SOD活性降低与MDA含量增加均有显著的调节作用.

Ethnopharmacological relevance: Panax ginseng C. A. Meyer (ginseng) is a widely used traditional Chinese medicine that has played a beneficial role in the treatment of various diseases, including liver diseases. Ginsenoside Rg1 is a saponin isolated and purified from ginseng that exerts protective effects on the liver in some liver injury models. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous dioxin found mostly in food products that causes liver injury and other human diseases. Although significant efforts have been made to reduce the burden of liver disease, there is still a lack of effective treatment methods.Aim of the study: Although ginsenoside Rg1 was reported to inhibit TCDD-mediated cytochrome P450 1A1 (CYP1A1) induction in HepG2 cells, we sought to verify its hepatoprotective effects and elucidate its mechanism in a TCDD-induced liver injury model in mice.Material and methods: The mouse liver injury model was established by intraperitoneal TCDD injection, followed by treatment with various doses of ginsenoside Rg1 (50, 100, and 200 mg/kg). Clinical indicators of liver injury, such as an increase in serum aspartate aminotransferase and alanine aminotransferase levels, as well as histopathological changes were evaluated.Results: The common clinical indicators of liver injury were detected following TCDD injection, including an increase in serum alanine aminotransferase and aspartate aminotransferase levels, increased relative liver weight, and histopathological changes. Following treatment with ginsenoside Rg1, the levels of aspartate aminotransferase and alanine aminotransferase decreased significantly, and the liver histology was improved. In addition, ginsenoside Rg1 competitively inhibited TCDD-induced Cyp1a1 mRNA transcription through the modulation of aryl hydrocarbon receptor (AhR) nuclear translocation.Conclusion: Ginsenoside Rg1 is a potent partial AhR agonist that has potential as an effective medication for protecting against TCDD-associated liver injury.

目的 研究血栓通注射液抗博来霉素诱导肺纤维化模型大鼠的药效学.方法 将180只SD大鼠随机分为假手术组、模型组、吡非尼酮(阳性药,50mg·kg-1)组和血栓通注射液低、中、高剂量(注射液原液1、2、4mL·kg-1)组,每组30只,采用气管内注射博来霉素方法制备肺纤维化大鼠模型,于造模24 h后各给药组ip给药,并分别在造模7、14、28 d取材.观察大鼠一般状态、体质量、肺系数;应用DSI/BUXCO监测系统检测肺功能指标潮气量、气道阻力及肺顺应性变化;进行HE与Masson染色,光镜下观察肺组织病理变化;并采用酶联免疫吸附法(ELISA)检测大鼠肺组织中Ⅰ型胶原(COL-Ⅰ)和纤维黏连蛋白(FN)的水平.结果 通过对大鼠的一般情况观察,发现给予血栓通注射液后,肺纤维化模型大鼠的活动和精神状态均有改善.与模型组比较,吡非尼酮组、血栓通注射液组大鼠体质量显著增加(P＜0.01、0.001),大鼠肺系数显著降低(P＜0.05、0.01、0.001).肺功能结果显示,与模型组比较,造模7d时血栓通注射液中剂量显著上调动态肺顺应性(P＜0.01):造模14 d时血栓通注射液高剂量显著降低气道阻力(P＜0.05)和上调动态肺顺应性(P＜0.01);造模28 d时吡非尼酮和血栓通注射液中剂量均显著上调动态肺顺应性(P＜0.01).HE及Masson结果显示,吡非尼酮组、血栓通注射液组的肺纤维化程度明显轻于模型组.ELISA结果显示,与模型组比较,造模7 d时吡非尼酮组、血栓通注射液高剂量组大鼠肺组织中的FN显著降低(P＜0.01、0.001),吡非尼酮组COL-Ⅰ水平显著降低(P＜0.001);造模14 d时吡非尼酮组和血栓通注射液中、高剂量组大鼠肺组织中的COL-Ⅰ水平显著降低(P＜0.05、0.01),吡非尼酮组FN显著降低(P＜0.05);造模28 d时吡非尼酮组和血栓通注射液中、高剂量组大鼠肺组织中的COL-Ⅰ、FN水平显著降低(P＜0.05、0.01、0.001).结论 血栓通注射液可改善肺纤维化模型大鼠肺功能与肺部形态学病变,降低肺组织中COL-Ⅰ和FN水平,对肺纤维化大鼠产生保护作用.