丹蛭降糖胶囊对糖尿病大鼠肾脏的保护作用  

Nephroprotective Effect of Danzhi Jiangtang Capsule on Diabetic Rats and its Mechanism

作　　者：李艳[1] 卜文婕[1] 朱建梁[1] 方朝晖[2] 孙敏[1] 

机构地区：[1]安徽大学生命科学学院,合肥230601 [2]安徽中医学院第一附属医院,合肥230031

出　　处：《中国药学杂志》2015年第10期857-862,共6页Chinese Pharmaceutical Journal

基　　金：安徽省教育厅自然科学基金资助项目(KJ2013A027);安徽大学研究生学术创新研究项目(yqh100118);国家中医药管理局国家中医药临床研究基地建设项目(20081211);国家中医药管理局国家中医药临床研究基地业务建设项目(JDZX2012001)

摘　　要：目的研究丹蛭降糖胶囊(danzhi jiangtang capsule,DJC)对糖尿病大鼠肾脏的保护作用及其机制。方法 SD雄性大鼠通过高糖高脂饮食结合小剂量链脲佐菌素(streptozotocin,STZ)的方法建立糖尿病大鼠动物模型,选择造模成功的糖尿病大鼠随机分为模型组、丹蛭降糖胶囊低、高剂量(600,2 000 mg·kg-1)组,每组8只;正常对照组和模型组给予等量蒸馏水灌胃。连续给药8周后,大鼠取血处死,分离血清检测血脂、肾功能、氧化指标;取肾脏称重,并计算肾脏指数;并留取肾组织标本固定做HE和PAS染色;蛋白质印迹检法测肾组织中JAK2、STAT3及其磷酸化蛋白(p-JAK2、p-STAT3)的表达;取肾皮质匀浆,ELISA法检测炎性因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和单核细胞趋化蛋白-1(monocyte chemoattractant protein,MCP-1)水平。结果模型组大鼠空腹血糖(fasting blood-glucose,FBG)、血脂、肾脏指数、氧化指标均高于正常对照组(P<0.01),肾功能降低,光镜下肾组织有明显病理结构改变,肾组织肿瘤坏死因子-α、白细胞介素-6和单核细胞趋化蛋白-1水平显著增高(P<0.01),肾组织中p-JAK2、p-STAT3表达水平升高(P<0.05)。丹蛭降糖胶囊治疗组血脂降低,但对空腹血糖影响不明显,肾功能明显提高,氧化指标降低,肾组织病理改变亦明显减轻,大鼠肾组织pJAK2、p-STAT3和炎症因子表达下降。结论丹蛭降糖胶囊能改善糖尿病大鼠肾功能,其机制可能是通过抗氧化从而抑制JAK2/STAT3炎症信号通路的活化,而降低肾脏局部炎症因子的表达。OBJECTIVE To investigate the nephroprotective effect of danzhi jiangtang capsule（ DJC） on diabetic rats induced by streptozotocin（ STZ） and elucidate its mechanism. METHODS Model of diabetic rats were established by combination of high-fat diet-fed and low-dose STZ injection in SD rats. The successful models were chosen and randomly divided into model group,low-dose and high-dose of DJC（ 600,2 000 mg·kg- 1,ig） groups,each consisting of 8 rats. Control and model groups were administered equal volume of distilled water. After 8 weeks of treatment,the rats were killed and serum was separated to detect blood lipid,renal function and oxidative stress. The kidneys were weighed,and the renal indexes were calculated. Renal tissue specimens were fixed for HE and PAS staining; the expressions of JAK2,STAT3,p-JAK2,p-STAT3 in the kidneys were observed by Western blot; the renal inflammatory factors TNF-α,IL-6 and MCP-1 were detected by ELISA. RESULTS Fasting blood glucose（ FBG）,blood lipid,renal index,oxidative stress of model group were significantly increased,renal function was reduced,and the morphology of renal tissue changed significantly. The renal inflammatory cytokine TNF-α,IL-6 and MCP-1 and the expressions of p-JAK2,p-STAT3 increased significantly in diabetes mellitus rats. After 8 weeks of treatment,blood lipid and oxidative stress in DJC groups were decreased,but there was no obvious difference in FBG between DJC groups and model group,the renal function and the pathological changes of renal tissue were improved obviously. The expressions of inflammatory cytokine（ TNF-α,IL-6 and MCP-1）,p-JAK2 and p-STAT3 in renal cortex were significantly down-regulated. CONCLUSION The nephroprotective effect of DJC is based on its antioxidant effect and anti-inflammatory effect via suppression of JAK2 / STAT3 signal transduction.

关 键 词：丹蛭降糖胶囊 糖尿病肾病 氧化应激 炎症因子 JAK2/STAT3信号通路 

分 类 号：R965[医药卫生—药理学]