Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

Comparative Observation on the Effects of Radix Tripterygium Hypoglaucum Tablet and Tripterygium Glycosides Tablet in Treating Erosive Oral Lichen Planus

Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.

Characteristics and pharmacokinetics of tripterygium glycosides nano-carries transdermal delivery systems:skin-blood synchronous microdialysis and numerical simulation

The traditional Chinese medicine tripterygium glycosides(TPG)is used clinically to treat some Rheumatism,Eczema,immunosuppression and tumor,with the activities of hypnosis,antipyretic,analgesic,antiinflammatory,allergy and antitumor.However TPG has low water solubility and low skin permeability,so its clinical use is limited.Transdermal delivery systems can provide a controlled drug release rate that can keep constant concentrations of drug in the plasma for up to multiple days,improved patient compliance,and the possibility ofreducing the rate and severity of side effects.In this study,a fast and sensitive technique skin-blood two sites synchronous microdialysis coupled with LC-MS was used to study the pharmacokinetic parameter of three different formulations(TPG nanoemulsion,TPG nanoemulsion based gels and TPG gel).Creating a multilayer model,use the model to simulate the three formulations dynamics in transdermal-drug delivery system.The experiment results showed that the TPG nanoemulsion,TPG nanoemulsion based gels can significantly raise the drug concentrations in skin more than that of TPG gels.The numerical simulation results indicating that TPG gel and TPG nanoemulsion are close to practical measurements,only in the concentration increase phase the numerical simulation result has some difference with the experimental results.TPG nanoemulsion based gels have significant difference with the experimental results,both in concentration increase stage and concentration decreasing stage,but its trend was same.The study shows that the skin-blood synchronous microdialysis technique provided a new method for the pharmacokinetics study of nanocarriers transdermal delivery systems.In addition,the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery system.

Anti-angiogenic effect of tripterygium glycosides tablets in animal models of rheumatoid arthritis:A systematic review and meta-analysis

Objectives:To explore and summarize the beneficial effects of a traditional Chinese medicine preparation,Tripterygium glycosides tablets(TGT),in rheumatoid arthritis(RA)animal models of neovascularization,and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods:We searched the databases PubMed,Embase,Web of Science,Chinese National Knowledge Infrastructure,VIP,Wan Fang and SinoMed(China Biomedical Document Service System)to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April2020.Subgroup analysis and meta-regression were performed for dosage and duration of TGT.Statistical tests and subgroup analysis were conducted using RevMan 5.3,and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0.Results:Fourteen studies of TGT in RA rats were included in this analysis.Treatment with TGT significantly reduces synovial microvessel density and the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2,hypoxia inducible factor a,c-Fos,c-Jun,angiopoietin-1 and angiopoietin-2 compared with control groups(P<.05).Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium,assessed using quantitative real-time PCR,with duration or dosage of TGT.Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels.Sensitivity analysis on VEGF m RNA levels did not fundamentally change the results.Conclusions:TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF,VEGF receptor 2,hypoxia-inducible factor a,c-Fos,c-Jun,Ang-1 and Ang-2,thereby suppressing pannus formation and bone destruction in rat models of RA.Additional well-designed studies are required to confirm these findings.

A Synoptical Introduction of The Clinical Application of Tripterygium Glycosides

Tripterygium glycosides (TG) refers to the total glycosides, mainly the epoxy diterpene lactones extracted from the root of Tripterygium Wilfordii Hook f (TW), a common vine-like toxic plant grown in the wide area of South China. It possesses potent anti-inflammatory and immune suppressive effects and also some anti-coagulation and bacteriocidal action, and compared with other preparations of TW, it shows the superiority of being small in dose and having less adverse effect. It has been reported to be effective in treating patients with such diseases as rheumatoid arthritis, lupus or purpura nephritis, psoriasis, erythroderma, and allergoses. This article is attended to synoptically introduce the recent clinical applications of TG.

Alprostadil combined with tripterygium glycosides tablet in treatment of diabetic kidney disease: a systematic review and meta-analysis

Background:Diabetic kidney disease is now the principal cause of end-stage renal failure worldwide.Alprostadil combined with tripterygium glycosides tablet is a new method for diabetic kidney disease treatment.However,there are currently few systematic reviews on treatment for alprostadil combined with tripterygium glycosides tablet.Therefore,a systematic review and meta-analysis was conducted to analyze the function of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease.Methods:We searched Pubmed,Embase,the Cochrane Library,Chinese databases,and clinical trial for randomized controlled trials of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease,including results from the foundation of database until August 5,2020.Two reviewers have independently performed literature screening,data extraction,and quality evaluation.This meta-analysis has been carried out by RevMan5.4 software.Results:Ten randomized controlled trials with 724 patients were involved.Compared with alprostadil alone,the combination of alprostadil and tripterygium glycosides tablet in treatment of diabetic kidney disease could reduce the level of 24-hour urine protein(95%CI(–2.05,–0.22),P=0.01),serum creatinine(95%CI(–5.01,–0.20),P=0.03),level of interleukin-6(95%CI(−4.57,−2.37),P<0.00001),tumor necrosis factor-α(95%CI(−4.57,−2.37),P<0.00001).The combined treatment could also improve the clinical efficacy(95%CI(1.09,1.25),P<0.0001),and reduce the occurrence of serious adverse events(95%CI(0.26,0.94),P=0.03).However,there is no association of two treatments in blood urea nitrogen(95%CI(–4.17,2.11),P=0.52),albumin(95%CI(–1.10,0.97),P=0.90),triglyceride(95%CI(−1.44,1.50),P=0.97).Conclusion:Alprostadil combined with tripterygium glycosides tablet contributes to protecting renal function,inhibiting inflammation,and reducing the occurrence of adverse events,which could be considered as a feasible therapy for diabetic kidney disease patients.However,some clinical variables did not accurately conclude due to the low quality of methodology and small sample sizes.More rigorous and more extensive trials are essential to validate our results.Trial registration:Systematic review registration:(CRD42020203725).

Study on Effect of Small Dosage Tripterygium Glycosides in Auxiliary Treatment of Intractable Still's Disease

Intractable Still’s disease, namely the intractable systemic juvenile idiopathic arthritis (JIA) is a clinical difficulty of pediatrics, and so far there still lacks any special treatment. In virtue of the markedly anti-inflammatory and immunosuppres-sive effects of tripterygium glycosides (TG, product of Huangshi Pharmaceutical Factory, 10 mg/

CLINICAL STUDY ON EFFECT OF TRIPTERYGIUM WILFORDII HOOK. F. GLYCOSIDES ON UTERINE LEIOMYOMA

Objective To observe the therapeutic effect and side reactions of Tripterygium wilfordii Hook,f. ( GTW) glycosides on patients with uterine leiomyomas. Methods 65 normally cycling women with symptomatic uterine leiomyomas received 40mg daily dose GTW for 3 to 6 months. Baseline ultrasound tests were obtained to evaluate the sizes of myomas and uterus, then repeated three and six months after treatment. Blood samples were collected to determine the hormonal levels of in the mid-follicular and mid-luteal phases of the menstrual cycles before GTW therapy and at 3~4 months and 5~6 months after treatment. Results Significant decrease in leiomy-oma volume was shown in 39 of 65 (60% ) and 28 of 40 ( 70% ) patients after 3~4 months and 5~6 months of treatment, respectively. The decrease of the volume of leiomyoma was time-dependent as while 27. 84% and 51.60% in 3~4 months and 5 ~ 6months, respectively. 25 of 65 patients had amenorrhea during the course of treatment. Tripterygium wilfordii glycosides treatment induced a significant increase in LH and FSH levels (P < 0. 01) as compared with pretreatment values. In contrary, a significant decrease in E2 and P levels (P <0. 05) was found, but no changes were observed in T and PRL levels after treatment. Conclusion Tripterygium wilfordii might serve as an effective therapeutic agent for leiomyomas with fewer side effects. A reversible inhibitory effect on the ovary by Tripterygium wilfordii glycosides may be one of the mechanisms of Tripterygium wilfordii in decreasing leiomyoma volume.

A Dietary Supplement Jinghuosu Ameliorates Reproductive Damage Induced by Tripterygium Glycosides

Objective To determine the possible protective effects of Jinghuosu,a dietary supplement(DS),on tripterygium glycosides(TG)-induced reproductive system injury in rats and its underlying mechanisms.Methods A reproductive damage model was established in rats by feeding of TGs.Twenty-eight male Sprague Dawley rats were randomly divided into 4 groups using a random number table(n=7 in each):control(C)group,model(M)group,DS group and L-carnitine(LC)group.Rats in M,DS and LC groups received 40 mg/kg TGs orally.Starting from the 5th week,after administration of TGs for 4 h every day,rats in DS and LC groups were administered with 2.7 g/kg DS and 0.21 g/kg LC,respectively,for protective treatment over the next 4 weeks.Rats in Group C continued to receive the control treatment.Hematoxylin-eosin staining was used for histopathological analysis of rat testicular tissues.Enzyme-linked immunosorbent assay was performed to measure alkaline phosphatase(ALP),lactate dehydrogenase,alcohol dehydrogenase,total antioxidant capacity(T-AOC),superoxide dismutase,glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)concentrations.Chemiluminescence assay was used to determine the serum testosterone content.Quantitative real-time PCR and Western blotting were conducted to analyze the expression of genes and proteins related to the testosterone synthesis pathway and the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 antioxidant pathway.Results Oral administration of TGs induced significant increases in the testicular levels of zinc transporter 1 and MDA(P<0.05).On the other hand,sperm concentration,sperm motility,and serum testosterone,serum zinc,testicular zinc,Zrt-,Irt-like protein 1,ALP,luteinizing hormone(LH)receptor,steroidogenic acute regulatory protein,Cytochrome P450 family 11 subfamily A member 1,3β-hydroxysteroid dehydrogenase 1 T-AOC,GSH-Px,nuclear factor erythroid 2-related factor 2,heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1 levels decreased following TGs exposure(P<0.05).All of these phenotypes were evidently reversed by DS(P<0.05).Conclusion DS Jinghuosu protects against TG-induced reproductive system injury in rats,probably by improving zinc homeostasis,enhancing the testosterone synthesis and attenuating oxidative stress.

雷公藤多苷片对IgA肾病大鼠LIGHT-HVEM/LTβR通路的影响

目的 基于炎症相关通路探讨雷公藤多苷片对IgA肾病大鼠肾脏的作用机制。方法 雄性SPF级SD大鼠,随机分为空白组、造模组。造模组采用联合“牛血清白蛋白+四氯化碳+脂多糖”建立IgA肾病大鼠模型。造模成功的大鼠随机分为模型组、泼尼松组、雷公藤多苷片组,于第13周开始治疗组灌胃给药,给药4周后留取大鼠24 h尿液、血液、肾组织并检测尿红细胞数、24 h-UTP、BUN、Scr;ELISA检测血清IL-1β、TNF-α水平;HE染色观察各组大鼠肾组织病理学变化;Western blot及RT-PCR检测大鼠肾组织LIGHT、HVEM、LTβR蛋白及其mRNA的表达。结果 雷公藤多苷片明显降低IgA肾病大鼠尿红细胞数、24 h-UTP、BUN、Scr水平,改善肾组织病理,降低血清炎症因子IL-1β、TNF-α水平,降低肾组织中LIGHT、HVEM、LTβR蛋白及其mRNA表达水平。结论 雷公藤多苷片可能通过下调LIGHT-HVEM/LTβR信号通路,抑制免疫反应,减少炎症因子释放,从而减轻炎症反应,降低尿红细胞及尿蛋白,改善肾脏病理损伤,保护肾功能。

雷公藤多苷纳米粒的制备及其对关节炎大鼠的治疗作用

目的 制备雷公藤多苷纳米粒,探究其对胶原诱导型(collagen-induced arthritis, CIA)关节炎大鼠的治疗作用。方法 运用薄膜分散法制备雷公藤多苷纳米粒,对其进行质量评估。构建CIA模型,进行药物干预,称量大鼠体质量、测定足趾肿胀度和关节炎指数;观察大鼠脏器、膝、踝关节滑膜的病理改变;检测大鼠血清中肝肾功能水平和炎症因子表达。结果 制备的雷公藤多苷纳米粒在电镜下呈圆粒状且分布均匀,性质稳定。相较于模型组,给药组大鼠左右足趾肿胀度均明显下降(P<0.01),关节炎指数明显降低(P<0.01)。其中TG-NPs组的疗效优于TG组。与正常组相比,大鼠心脏、脾、肾、睾丸指数均明显降低(P<0.05,P<0.01)。TG-NPs组膝踝关节软骨病理损伤明显减轻,凋亡的滑膜细胞增加;与模型组相比,TG-NPs组大鼠血清中的ALT、BUN、CRE水平均明显降低(P<0.05),IL-1β、TNF-α和IL-6含量下降明显(P<0.05)。结论 TG-NPs通过诱导滑膜细胞凋亡和降低炎性细胞因子的表达对CIA有较好的治疗作用,通过静脉注射血液循环,可实现药物的缓、控释,避免口服药物造成的首过效应,减轻脏器的毒性,为治疗类风湿关节炎的新型纳米制剂的开发提供了实验依据。

五子衍宗丸对雷公藤多苷致肾病综合征雄鼠生殖损伤的机制研究

目的:观察五子衍宗丸干预肾病综合征SD大鼠对生精细胞T型Ca^(2+)通道及顶体酶PPEF1活性的影响及作用机制。方法:按照随机数字表法将70只SD大鼠分为空白组(蒸馏水1 mL灌胃)、肾病模型组(蒸馏水1 mL灌胃)、肾病模型+雷公藤多苷组(雷公藤多苷0.04 mg·kg^(-1)·d^(-1)灌胃)、肾病模型+五子衍宗丸组(五子衍宗丸1.07 g·kg^(-1)·d^(-1)灌胃)、肾病模型+雷公藤多苷+低剂量五子衍宗丸组(雷公藤多苷0.04 mg·kg^(-1)·d^(-1)与五子衍宗丸0.54 g·kg^(-1)·d^(-1)同时灌胃)、肾病模型+雷公藤多苷+中剂量五子衍宗丸组(雷公藤多苷0.04 mg·kg^(-1)·d^(-1)与五子衍宗丸1.07 g·kg^(-1)·d^(-1)同时灌胃)、肾病模型+雷公藤多苷+高剂量五子衍宗丸组(雷公藤多苷0.04 mg·kg^(-1)·d^(-1)与五子衍宗丸2.14 g·kg^(-1)·d^(-1)同时灌胃)。通过鼠尾静脉注射阿霉素造成肾病综合征模型,除空白组外,其余各组于实验第1天和第8天分别鼠尾静脉注射阿霉素,第1天以4.0 mg/kg剂量注射、第8天以3.5 mg/kg剂量注射。实验各组连续灌胃干预30 d。采用膜片钳放大法记录生精细胞T型Ca^(2+)通道电流变化情况;ELISA法测定顶体酶PPEF1活性;ELISA法测定血清中促性腺激素释放激素(GnRH)、雌二醇(E2)、促卵泡激素(FSH)、睾酮(T)和黄体生成素(LH)水平;荧光标记法测定顶体反应发生率。结果:与空白组比较,肾病模型组生精细胞T型Ca^(2+)活性降低(P<0.01)、顶体酶PPEF1活性降低(P<0.05)、性激素GnRH、E2、T水平降低(P<0.05),性激素FSH、LH水平升高(P<0.05);与肾病模型组比较,肾病模型+雷公藤多苷组生精细胞T型Ca^(2+)活性降低(P<0.01)、顶体反应发生率降低(P<0.05),性激素T水平降低(P<0.05),性激素FSH水平增高(P<0.05);与肾病模型+雷公藤多苷组比较,肾病模型+雷公藤多苷+中剂量五子衍宗丸组T型Ca^(2+)活性升高、顶体酶PPEF1活性升高、顶体反应发生率升高、性激素GnRH、E2、T水平升高,FSH、LH水平降低(P<0.05);与肾病模型+雷公藤多苷+低剂量五子衍宗丸组比较,肾病模型+雷公藤多苷+中剂量五子衍宗丸组、肾病模型+雷公藤多苷+高剂量五子衍宗丸组T型Ca^(2+)活性升高、性激素T水平升高(P<0.05)。结论:五子衍宗丸可以提高生精细胞T型Ca^(2+)电流、顶体酶PPEF1活性,促进顶体反应的发生,五子衍宗丸可以防治雷公藤多苷在肾病综合征治疗中的致不育副作用。

五子衍宗丸对肾病综合征雄鼠生殖功能的保护作用

目的五子衍宗丸干预雷公藤多苷治疗肾病综合征,探究五子衍宗丸对肾病综合征大鼠生殖能力、肾脏功能的影响。方法以雄性SD大鼠为研究对象,按照随机数字表法将70只大鼠分为空白组、肾病模型组、肾病模型+雷公藤多苷组、肾病模型+五子衍宗丸组、肾病模型+雷公藤多苷+低剂量五子衍宗丸组、肾病模型+雷公藤多苷+中剂量五子衍宗丸组、肾病模型+雷公藤多苷+高剂量五子衍宗丸组。于实验第1天和第8天需造模各组分别鼠尾静脉注射阿霉素4.0、3.5 mg/kg造肾病综合征模型。从实验第1天开始实验各组连续灌胃干预30 d。采用全自动生化仪器检测血清尿素氮、血肌酐、24 h尿蛋白定量、总胆固醇、甘油三酯、血浆白蛋白;采用ELISA检测血清中GnRH、E_(2)、FSH、T和LH等激素水平。观察肾脏和睾丸的病理改变。结果睾丸病理结果显示与单独接受雷公藤多苷治疗的组别比较,加入五子衍宗丸的各组生精小管萎缩减轻,管腔空泡减少,各层生精细胞层数增多,生精细胞数目增多。肾脏病理结果显示联合应用雷公藤多苷和五子衍宗丸治疗的组别较单独应用雷公藤多苷或五子衍宗丸的组别肾小球硬化、肾小管损伤、肾间质纤维化和炎症细胞浸润等病理改变降低。与肾病模型组比较,肾病模型+雷公藤多苷组性激素T降低,FSH增高;与肾病模型+雷公藤多苷组比较,肾病模型+五子衍宗丸组性激素GnRH、E_(2)、T增高,FSH、LH降低;与肾病模型+雷公藤多苷组比较,肾病模型+雷公藤多苷+中剂量五子衍宗丸组、肾病模型+雷公藤多苷+高剂量五子衍宗丸组性激素GnRH、T增高,FSH、LH降低;与肾病模型+雷公藤多苷+低剂量五子衍宗丸组比较,肾病模型+雷公藤多苷+中剂量五子衍宗丸组、肾病模型+雷公藤多苷+高剂量五子衍宗丸组性激素T增高。与肾病模型组比较,肾病模型+雷公藤多苷+中剂量五子衍宗丸组、肾病模型+雷公藤多苷+高剂量五子衍宗丸组血清肌酐含量降低、血浆白蛋白含量升高。结论通过在雷公藤多苷治疗肾病综合征的基础上添加五子衍宗丸,观察到在肾脏和睾丸的病理、生化指标以及性激素水平方面,相较于未添加五子衍宗丸的组别,病变程度较轻。这表明五子衍宗丸能够有效治疗肾病综合征,并对男性不育问题产生积极影响。这一研究为同时处理肾病综合征和男性不育提供了新的治疗思路。

不同剂量雷公藤总苷联合西药治疗类风湿性关节炎疗效比较

目的探讨不同剂量雷公藤总苷联合美洛昔康片治疗类风湿性关节炎的疗效及安全性。方法选择80例类风湿性关节炎患者,按照随机数表法分为大剂量组与小剂量组,各40例。2组均给予美洛昔康片治疗,大剂量组给予每次20 mg雷公藤总苷,小剂量组给予每次10 mg雷公藤总苷,2组均治疗2个月。比较2组临床疗效;治疗前、治疗2个月后,比较2组关节功能障碍分级、晨僵时间、关节视觉模拟疼痛评分(VAS)、双手平均握力、关节压痛数、关节肿胀数及白细胞介素-6(IL-6)、红细胞沉降率(ESR)、类风湿因子(RF)、C-反应蛋白(CRP)水平;观察2组不良反应发生情况。结果大剂量组临床疗效优于小剂量组(P<0.05)。治疗后,大剂量组关节功能障碍分级I级人数明显多于小剂量组(P<0.05),Ⅲ级人数明显少于小剂量组(P<0.05);大剂量组晨僵时间、VAS评分、关节压痛数、关节肿胀数水平、IL-6、ESR、RF、CRP水平低于小剂量组(P<0.05),双手平均握力水平高于小剂量组(P<0.05)。2组不良反应发生情况比较,大剂量组发生不良反应略多于小剂量组,差异无统计学意义(P>0.05)。结论大剂量雷公藤总苷联合美洛昔康片的疗效优于小剂量雷公藤联合美洛昔康片,能够有效减轻患者临床症状,降低炎症因子水平,但有可能增加不良反应发生风险,临床需要根据实际情况调整雷公藤总苷给药量。

网络药理学结合分子对接技术分析雷公藤甲素治疗内异症的机制

目的 选取雷公藤多苷的主要活性物质雷公藤甲素,基于网络药理学结合生物信息分析及分子对接分析雷公藤甲素治疗子宫内膜异位症(endometriosis, EMS)的潜在靶点和通路。方法 通过ChEMBL平台进行雷公藤甲素靶点收集,通过OMIM、TTD、PharmGKB数据库找出EMS的靶点;取药物靶点和疾病靶点两者的交集构建PPI网络,利用Cytoscape软件及R包筛选出核心靶点;使用string在线平台对核心靶点进行GO分析和KEGG分析。使用分子对接和生物信息分析对关键靶点进行进一步验证。结果 雷公藤甲素与EMS的共同靶点有73个,筛选出核心靶点13个,GO和KEGG富集分析发现生殖器官的发育、凋亡信号通路的调控、类固醇激素及其受体的生物功能及内分泌抵抗通路最为相关。结论 预测了雷公藤甲素治疗EMS的核心靶点、生物学过程以及关键信号通路,将有助于更好地理解雷公藤多苷在EMS治疗中的机理,为其基础研究提供一些参考。

雷公藤多苷调控miR-496表达对高糖诱导的人肾足细胞泛素化通路的影响

目的探究雷公藤多苷调控miR-496表达对高糖诱导的人肾足细胞泛素化通路的影响。方法将人肾足细胞分为NC组、HG组、TWP-L组、TWP-M组、TWP-H组、miR-496组、miR-NC组、TWP-H+anti-miR-496组。CCK-8检测细胞增殖;流式细胞仪检测细胞凋亡;蛋白质印迹检测细胞中p53、COP1、caspase-3、nephrin、podocin蛋白表达;qRT-PCR检测细胞中miR-496表达。结果与NC组比较,HG组细胞存活率、细胞中miR-496表达(0.23±0.04)和COP1(0.43±0.05)、nephrin(0.24±0.03)、podocin(0.31±0.04)蛋白表达均明显降低,细胞凋亡率(23.94±2.46)、细胞中p53(1.26±0.15)、caspase-3(0.61±0.08)蛋白表达均明显增加(P<0.05);与HG组比较,TWP-L组、TWP-M组、TWP-H组细胞存活率、细胞中miR-496表达和COP1、neph-rin、podocin蛋白表达均明显增加,细胞凋亡率、细胞中p53、caspase-3蛋白表达均明显降低(P<0.05);与miR-NC组相比,miR-496组细胞存活率、细胞中miR-496表达(0.87±0.10)和COP1(0.80±0.09)、nephrin(0.58±0.06)、podocin(0.75±0.08)蛋白表达明显增加,细胞凋亡率(10.61±1.17)、细胞中p53(0.32±0.04)、caspase-3(0.25±0.03)蛋白表达明显降低(P<0.05);与TWP-H组相比,TWP-H+ant-miR-496组细胞存活率、细胞中miR-496表达(0.18±0.02)和COP1(0.46±0.06)、nephrin(0.31±0.04)、podocin(0.34±0.04)蛋白表达明显降低,细胞凋亡率(20.36±2.18)、细胞中p53(1.19±0.13)、caspase-3(0.57±0.06)蛋白表达明显升高(P<0.05)。结论雷公藤多苷可能通过促进miR-496表达,对高糖诱导的人足细胞泛素化蛋白酶通路的活化发挥促进作用,对足细胞的凋亡发挥抑制作用。

雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征的效果及对血清sTNF-R1、IGFBP-2、CFH水平的影响

目的 探讨雷公藤多苷联合他克莫司及激素治疗难治性肾病综合征(RNS)的疗效对血清可溶性肿瘤坏死因子受体1(s TNF-R1)、胰岛素样生长因子结合蛋白-2(IGFBP-2)、补体因子H(CFH)水平的影响。方法 研究对象为2018年8月至2021年8月于江南大学附属医院治疗的RNS患者102例,以随机数字表法分为对照组(n=51,采取甲泼尼龙片加他克莫司胶囊治疗)和观察组(n=51,在对照组基础上给予雷公藤多苷片治疗)。评估两组的治疗效果、血清相关指标,统计两组的不良反应。结果 观察组治疗总有效率(96.08%)高于对照组(80.39%)(χ^(2)=6.044,P=0.014);治疗后,观察组患者血清白蛋白、CFH水平[分别为(36.54±8.11) g·L^(-1)、(586.20±100.72)μg·m L^(-1)],高于对照组[分别为(32.58±6.12) g·L^(-1)、(540.11±100.47)μg·m L^(-1)],差异均有统计学意义(t=2.783,P=0.006;t=2.314,P=0.023);观察组患者24 h尿蛋白、肌酐、s TNF-R1、IGFBP-2水平[分别为(2.67±0.69) g、(82.25±16.13)μmol·L^(-1)、(1.56±0.45) ng·m L^(-1)、(51.34±10.44) ng·m L^(-1)],低于对照组[分别为(3.24±1.02) g、(92.68±17.35)μmol·L^(-1)、(1.91±0.58) ng·m L^(-1)、(57.79±12.58) ng·m L^(-1)],差异均有统计学意义(t=3.306,P=0.001;t=3.135,P=0.002;t=3.405,P=0.001;t=2.820,P=0.005);观察组复发率(1.96%)低于对照组(13.73%)(χ^(2)=4.883,P=0.027)。结论 公藤多苷联合他克莫司及激素治疗RNS效果佳,降低复发率,改善肾功能,减轻炎症,有望作为辅助治疗RNS的药物。

雷公藤多苷联合托法替布治疗类风湿关节炎临床研究

目的:观察雷公藤多苷联合托法替布治疗类风湿关节炎(RA)的临床疗效。方法:采用随机数字表法将82例RA患者分为对照组与观察组各41例。对照组给予托法替布治疗,观察组给予雷公藤多苷联合托法替布治疗。比较2组治疗前后临床症状相关参数及细胞因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、核因子κB受体活化因子配体(RANKL)、C-反应蛋白(CRP)、血沉(ESR)]水平,评估2组临床疗效及不良反应发生情况。结果:观察组总有效率95.12%,高于对照组80.49%(P<0.05)。2组治疗后关节压痛数、关节肿胀数、视觉模拟评分法(VAS)评分及TNF-α、IL-6、RANKL、CRP、ESR水平均较治疗前降低(P<0.05),晨僵时间缩短(P<0.05);观察组治疗后关节压痛数、关节肿胀数、VAS评分及细胞因子水平均低于对照组(P<0.05),晨僵时间少于对照组(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:雷公藤多苷联合托法替布治疗RA疗效显著,能够改善患者临床症状,抑制炎症反应,安全性较高。

当归芍药散对果蝇生殖功能损伤模型的改善作用

目的建立果蝇生殖功能损伤模型,观察当归芍药散(DSS)是否具有改善作用。方法利用雷公藤多苷构建果蝇生殖功能损伤模型,统计子代成虫数量、亲代超氧化物歧化酶(SOD)及过氧化氢酶(CAT)活性、亲代生殖相关基因的表达、F1代体质量、F1代发育相关基因,评价DSS药效。结果20 mg·mL^(-1)雷公藤多苷可显著抑制子代数(P<0.01),可用于建立果蝇生殖功能损伤模型。与模型对照组相比,中(10 mg·mL^(-1))、大(20 mg·mL^(-1))剂量DSS可显著增加果蝇子代成虫数量(P<0.01,P<0.05);大剂量DSS显著提高了果蝇亲代SOD及CAT活性(P<0.01);中、大剂量DSS可促进果蝇亲代生殖相关基因表达,其中中剂量DSS可使DEAD-Box解旋酶4(VASA)、生殖系α因子(Figla)mRNA表达增加(P<0.05,P<0.01),大剂量可使VASA、Figla和叉头盒转录因子(FoxO)mRNA表达增加(P<0.01);中剂量DSS组F1代雌性果蝇体质量显著提高(P<0.05),大剂量DSS组F1代雌、雄果蝇体质量均显著提高(P<0.05,P<0.01);中、大剂量DSS均可显著提高F1代发育相关基因哺乳动物雷帕霉素靶基因(mTOR)mRNA表达(P<0.01)。结论DSS能够改善雷公藤多苷诱导的果蝇生殖功能损伤。