肾康丸对2型糖尿病大鼠TNF-α/IL-6/p-STAT3信号通路的影响

Effect of Shenkang Pill on Signal Transduction Pathway of TNF-α/IL-6/p-STAT3 in Type 2 Diabetic Rats

目的:通过观察肾康丸对2型糖尿病(DM)大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及肾脏磷酸化信号转导和转录活化因子-3(p-STAT3)表达的影响,探讨其防治糖尿病肾病(DN)的分子生物学机制。方法:采用高脂高糖喂养加腹腔注射30mg/kg链脲佐菌素(STZ)制备2型DM大鼠模型,大鼠随机分为4组:正常对照组(C组)、模型对照组(M组)、依那西普治疗组(DE组)、肾康丸治疗组(DS组)。各组分别干预8周后,检测大鼠尿α1-微球蛋白(Uα1-MG)、血清尿素氮(BUN)、血肌酐(C)r、TNF-α、IL-6水平及p-STAT3蛋白表达。结果:应用肾康丸、依那西普干预后,大鼠一般状况改善,Uα1-MG、BUN、Cr、TNF-α、IL-6水平较模型对照组显著减少(P<0.01),肾组织p-STAT3表达显著降低。结论:肾康丸对2型DM大鼠具有显著的肾保护作用,其作用机制可能与降低大鼠血清TNF-α、IL-6水平,从而影响其下游信号的转导,进而减少肾组织p-STAT3的表达有关。

Objective： To observe the effect of Shenkang Pill on the serum tumor necrosis factor alpha （TNF-α） and interleukin-6 （IL-6） levels, and the expressions of phosphorylation signal transduction activating factor-3 （p-STAT3） in the renal tissues of type 2 diabetic rats, and to explore the molecular therapeutic mechanism in preventing and curing diabetic nephropathy （DN）. Methods. The diabetic rat models were induced by the diet with high fat and glucose, and with the intraperitoneal injection of streptozotocin （STZ, 30mg/kg）. Then all rats were randomly divided into 4 groups： the normal group, the model group, Etanercept treatment group and Shenkang Pill treatment group. All rats were administered with gastric gavage of the corresponding drugs daily for 8 weeks. The urine a 1-microglobulin（U α 1-MG）, blood urea nitrogen （BUN） and serum creatinine （Cr） levels were measured by automatic biochemical analyzer, and TNF- a and IL-6 were detected by enzyme linked immunosorbent assay （ELiSA）. The expressions of p-STAT3 in the renal tissues were detected by Western blot method. Results; In diabetic rats, Shenkang Pill and etanercept ameliorated the rat general health state, reduced the levels of U a 1-MG, BUN, Cr, TNF-α and IL-6（P 〈 0.01）, and decreased the expressions of p-STAT3 in the renal tissue. Conclusion= Shenkang Pill has protective effect on the renal tissue of type 2 diabetic rats, which may be partly related to the decrease of the serum concentrations of TNF- α and IL-6, and with the reduction of the expressions of p-STAT3 in renal tissues.