灵芝多糖对链脲佐菌素诱导的糖尿病肾病小鼠抗炎活性及疗效研究
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国家自然科学基金(31471699);南京市属高校“十三五”重点学科建设项目(4217025)


Study on anti⁃inflammatory and therapeutic properties of Ganoderma lucidum polysacch⁃arides on diabetic nephropathy in streptozotocin⁃induced mice
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    摘要:

    目的:探讨灵芝多糖(Ganoderma lucidum polysaccharides,GL-PS)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病小鼠的疗效及机制。方法:STZ 100 mg/(kg·d)腹腔注射诱导糖尿病肾病小鼠模型,并随机分为6组:正常组、模型组、模型给药组(50、100、200 mg/kg GL-PS)、阳性对照组[5 mg/kg替米沙坦(telmisartan,TMS)],每组10只,连续灌胃给药8周后,收集动物的尿液、血液和肾脏,并使用试剂盒检测相关指标。以苏木精-伊红(hematoxylin-eosin,HE)染色对肾组织进行病理学检验,Western blot法检测小鼠肾组织中NOD样蛋白3(NOD-like receptor 3,NLRP3)、核因子(nuclear factor,NF)-κB及 白介素(interleukin,IL)-1β的蛋白表达。结果:GL-PS和TMS显著降低STZ诱导的糖尿病肾病小鼠血清中尿素氮(blood urea nitrogen,BUN)、肌酐(serum creatinine,SCr)、尿酸(serum uric acid,SUA)、血糖(glucose,GLU)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)及白介素(interleukin,IL)-1β、IL-18、IL-6 和肿瘤坏死因子(tumor necrosis factor,TNF)-α的水平;显著提高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)水平;24 h 尿蛋白排泄量亦明显较模型组降低;HE 染色及Western blot表明 GL-PS和TMS显著减轻炎症因子对肾组织的损伤,抑制NLRP3/NF-κB炎性小体的活化,下调IL-1β蛋白表达。结论:GL-PS对糖尿病肾病具有显著疗效,其机制可能与抑制炎症因子活化,改善肾功能有关。

    Abstract:

    Objective:To study the therapeutic properties and possible mechanism of Ganoderma lucidum polysaccharides(GL-PS)on diabetic nephropathy in streptozotocin(STZ)-induced mice. Methods:STZ[100 mg/(kg·d)] was administered by intraperitoneal injection to induce diabetic nephropathy model in mice. The mice were randomly divided into 6 groups(n=10 in each group):the normal group,model group,GL-PS groups with GL-PS dose of 50,100 and 200 mg/kg,and the telmisartan(TMS)group(5 mg/kg). After 8 continuous weeks of intragastric administration,the mice uric,blood and renal were collected,and some physiological and biochemical indexes were determined by kits. Renal pathology was examined by hematoxylin-eosin(HE)staining. Protein expressions of NOD-like receptor 3(NLRP3),nuclear factor(NF)-κB and interleukin(IL)-1β in renal tissues were also analyzed by Western blot. Results:Compared with the model group,GL-PS and TMS obviously decreased the levels of blood urea nitrogen(BUN),serum creatinine(SCr),serum uric acid(SUA),glucose(GLU),total cholesterol(TC),triglyceride(TG),and interleukin(IL)-1β,IL-18,IL-6,as well as tumor necrosis factor(TNF)-α and urinary protein contents excreted during 24 h;significantly increased the high-density lipoprotein cholesterol(HDLC)level in STZ-induced diabetic nephropathy mice. HE and Western blot results indicated that GL-PS and TMS also obviously alleviated renal inflammatory reaction,inhibited NLRP3/NF-κB inflammasome activation,and down-regulated the protein expression of IL-1β. Conclusion:GL-PS has remarkable therapeutic properties on diabetic nephropathy in mice. The possible mechanism may be related to suppressing of inflammasome activation and improving of renal function.

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马 静,芮海波,陈全战,汪振炯,陈玉胜.灵芝多糖对链脲佐菌素诱导的糖尿病肾病小鼠抗炎活性及疗效研究[J].南京医科大学学报(自然科学版),2019,(3):326-331

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  • 收稿日期:2018-04-12
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  • 在线发布日期: 2019-04-01
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