氯化两面针碱减轻糖尿病肾病模型大鼠的肾脏损伤  

Nitidine chloride alleviates renal injury in diabetic nephropathy rats

作　　者：刘树根 李泽玲[2] 罗新辉[2] 魏桂林[2] LIU Shu-gen;LI Ze-ling;LUO Xin-hui;WEI Gui-lin(Dept.of Drug Research,Quanzhou Stripping Pharmaceutical Factory,Quanzhou 362000;Dept.of Pharmacy,the First Affiliated Hospital of Gannan Medical College,Ganzhou 341000,China)

机构地区：[1]泉州罗裳制药厂药物研究中心,福建泉州362000 [2]赣南医学院第一附属医院药剂科,江西赣州341000

出　　处：《基础医学与临床》2018年第10期1422-1427,共6页Basic and Clinical Medicine

摘　　要：目的观察氯化两面针碱对糖尿病肾病大鼠肾脏的保护作用,并探讨其可能作用机制。方法将大鼠随机分为对照组、糖尿病肾病模型组(DN)、氯化两面针碱(NC)20和40 mg/kg干预组。在建模成功后灌胃氯化两面针碱,1次/d,一共给药7周。试剂盒检测血清中的胰岛素与胰高血糖素;过碘酸希夫(PAS)染色法观察肾脏组织病理形态学;原位末端标记法检测肾小球细胞凋亡;免疫印迹法检测肾组织中磷酸化Smad2与Smad3表达水平、TGF-β1与Smad7蛋白表达水平。结果 DN组大鼠的胰岛素含量低于对照组(P<0.05),胰高血糖素含量高于对照组(P<0.05);给予氯化两面针碱干预后,大鼠血清中的胰岛素含量增加,胰高血糖素含量下降;低剂量组肾脏的PAS染色呈弱阳性,可见弥漫性肾小球硬化,药物高剂量组无基底膜增厚及肾小管病变;肾组织中磷酸化Smad2与Smad3表达降低(P<0.05),TGF-β1与Smad7蛋白表达降低(P<0.05)。结论氯化两面针碱对糖尿病肾病大鼠肾脏具有一定程度的保护作用,其可能是通过抑制TGF-β/Smad信号通路发挥作用。Objective To observe the protective effects of nitidine chloride on renal injury in diabetic nephropathy rats, and to investigate the underlying mechanism. Methods All rats were divided into four groups： control group, diabetic nephropathy（DN） group, and diabetic nephropathy treated with nitidine chloride（NC） （20 mg/kg or 40 mg/kg ） groups. In addition to control group, the rest of the rats were induced for diabetic nephropathy model. After the animal model was successfully established, diabetic nephropathy rats were received nitidine chloride at the dose of 20 mg/kg or 40 mg/kg by gavage once a day for 7 weeks. The level of serum insulin and glucagon was determined by commercial detection kit. The pathological morphology of kidney tissues was observed by PAS staining. Cell apoptosis in glomerular was detected by TUNEL staining. The phosphorylation of Smad2 and Smad3 and the protein expression of TGF-β1 and Smad7 were analyzed by Western blot. Results After treated with nitidine chloride, insulin level in the serum was increased, whereas the glucagon level decreased. PAS staining showed that weak positive staining and diffuse glomerular sclerosis in low dose group. Moreover, no thickening matrix structure and renal tubular lesion could be observed in high dose group. Finally, Western blot showed that the phosphoryla- tion of Smad2 and Smad3 and the protein expression of TGF-β1 and Smad7 in kidney tissues were significantly decreased after nitidine chloride administration. Conclusions Nitidine chloride prevents renal injury in diabetic nephropathy rats through inhibition of TGF-β/Smad signaling pathway.

关 键 词：氯化两面针碱 糖尿病肾病 肾脏 TGF-Β/SMAD信号通路 

分 类 号：R587.1[医药卫生—内分泌]