甘露消渴胶囊通过JAK2/STAT3信号通路对糖尿病肾病大鼠的影响

Effect of Ganlu Xiaoke Capsule on JAK2/STAT3 signal pathway in rat model of diabetic nephropathy

关键词:  甘露消渴胶囊  链脲佐菌素  糖尿病肾病

Key words:  Ganlu Xiaoke Capsule  streptozotocin  diabetic nephropathy

摘要:

[目的] 研究甘露消渴胶囊对糖尿病肾病的治疗作用。[方法] 从70只雄性SD大鼠中随机选取10只作为空白对照组，其余大鼠用高脂高糖饲料喂养4周后腹腔注射链脲佐菌素（STZ，11 mg/mL，5 mL/kg），继续饲养4周，选取造模成功的42只大鼠随机分为4组，分别为模型组10只、甘露消渴胶囊低剂量组（0.93 g/kg生药）11只、甘露消渴胶囊高剂量组（1.86 g/kg生药）11只、二甲双胍合并缬沙坦组（180 mg/kg，14.4 mg/kg）10只。各给药组灌胃体积为10 mL/kg，空白对照组及模型组灌胃等体积的蒸馏水，治疗给药8周后测24 h尿蛋白，尾静脉采血测随机血糖，腹腔注射10%水合氯醛（3 mL/kg）麻醉，腹主动脉取血，检测血尿素氮（BUN）、血肌酐（Scr），最后取肾脏福尔马林溶液固定，用于苏木精-伊红（HE）染色和免疫组化技术检测JAK2、STAT3在肾脏组织的表达。[结果] 甘露消渴胶囊可显著降低JAK2及STAT3在糖尿病肾病大鼠肾脏组织表达，减轻糖尿病引起的肾小球增大及基底膜增生，减少糖尿病肾病大鼠尿蛋白、Scr及BUN的含量，且以上药理作用均与甘露消渴胶囊降低血糖的作用呈正相关。[结论] 甘露消渴胶囊可通过降低糖尿病大鼠随机血糖以及调控蛋白质酪氨酸激酶JAK2抗体（JAK2）、信号转导和转录激活因子3单克隆抗体（STAT3）在肾脏组织的表达，减轻高血糖对肾脏组织的病理损伤，改善肾功能，起到对糖尿病肾病大鼠肾脏的保护作用的作用。

Abstract:

[Objective] To study the therapeutic effect of Ganlu Xiaoke Capsule on diabetic nephropathy. [Methods] The 70 male SD rats,10 rats were randomly selected as the blank control group,and the remaining rats were fed with high-fat and high-sugar feed for 4 weeks,intraperitoneally injected with STZ(11 mg/mL,5 mL/kg),and kept feeding for 4 weeks. For the successful modeling,42 rats were randomly divided into 4 groups:10 model control group,11 Ganlu Xiaoke Capsule low-dose group(0.93 g/kg crude drug),and Ganlu Xiaoke Capsule high-dose group (1.86 g/kg crude drug) 11 rats,metformin combined with valsartan control group (180 mg/kg,14.4 mg/kg) 10 rats. The intragastric volume of each administration group was 10 mL/kg,the blank control group and the model control group were intragastrically given equal volumes of distilled water. After 8 weeks of treatment,urine protein was measured for 24 hours. Blood was collected from the tail vein to measure random blood glucose. 10% chloral hydrate (3 mL/kg) anesthetize,take blood from the abdominal aorta,test blood urea nitrogen (BUN),blood creatinine (Scr),and finally take the kidney and fix it with formal collar for HE staining. Immunohistochemical staining was used to detect the expression of JAK2 and STAT3 in kidney tissue. [Results] This study showed that Ganlu Xiaoke Capsule can significantly reduce the expression of JAK2 and STAT3 in the kidney tissue of the diabetic nephropathy rat models,reduce the glomerular enlargement and basement membrane hyperplasia caused by diabetes,and reduce the content of urine protein,Scr and BUN in diabetic nephropathy rat models,and the above pharmacological effects are positively correlated with the effect of Ganlu Xiaoke Capsule in lowering blood sugar. [Conclusion] Ganlu Xiaoke Capsule can reduce the random blood glucose level of diabetic rats and regulate the expression of JAK2 and STAT3 in the kidney tissues,reduce the pathological damage of high blood sugar to kidney tissue,improve kidney function,and ultimately produce a protective effect on the kidneys of diabetic rats.