大黄配方颗粒对庆大霉素诱导的肾损伤小鼠JAK2/STAT3信号通路的调节作用研究

Regulatory Effect of Rhubarb Formula Granule on JAK2/STAT3 Signal Pathway in Mice with Gentamicin-induced Renal Injury

目的:研究大黄配方颗粒(DHPK)对庆大霉素诱导的肾损伤小鼠JAK2/STAT3信号通路的调节作用。方法:90只小鼠随机分为对照组、模型组、DHPK低、中、高剂量组及阳性对照组,15只/组,采用腹腔注射庆大霉素建立肾损伤小鼠模型,DHPK低、中、高剂量组按照1、2、4 g/kg灌胃给予大黄配方颗粒,阳性对照组按照21.43 mg/kg灌胃给予小鼠维拉帕米,1次/d,连续28 d,检测小鼠24 h尿蛋白量及尿N-乙酰-β-D-葡萄糖苷(NAG)酶水平,血清尿素氮(BUN)及血肌酐(Scr)水平、肾组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)水平,苏木精-伊红(HE)染色法检查肾组织病理学变化,Western blot检测小鼠肾组织p-JAK2、JAK2、p-STAT3、STAT3水平。结果:与模型组比较,DHPK各剂量组小鼠24 h尿蛋白量及尿NAG酶水平,血清BUN、Scr水平、肾组织MDA水平及p-JAK2、JAK2、p-STAT3、STAT3水平均显著降低(P<0.05),肾组织SOD活性显著升高(P<0.05),小鼠肾组织病理学变化明显改善。结论:大黄配方颗粒能够恢复庆大霉素诱导的肾损伤小鼠肾功能,降低氧化应激损伤,其机制可能与调节JAK2/STAT3信号通路有关。

Objective:To study the regulatory effect of rhubarb formula granule(DHPK) on JAK2/STAT3 signal pathway in mice with gentamicin-induced renal injury.Methods:90 mice were randomly divided into control group,model group,low,middle and high dose groups of DHPK and positive control group,15 mice in each group.The rat model of renal injury was established by intraperitoneal injection of gentamicin.The low,middle and high dose groups of DHPK were given rhubarb formula granules according to the doses of 1,2 and 4 g/kg,respectively.Mice in the positive control group were given verapamil according to 21.43 mg/kg,once a day for 28 days.24-hour urinary protein and urine NAG enzyme levels,serum BUN,Scr levels,renal SOD activity and MDA levels were detected.Renal histopathological changes were examined by hematoxylin eosin staining.The levels of p-JAK2,JAK2,p-STAT3 and STAT3 in kidney tissue of mice were detected by Western blot.Results:Compared with the model group,the 24-hour urinary protein and the level of urinary NAG enzyme,the levels of serum BUN and SCr,the level of MDA in renal tissue and the levels of p-JAK2,JAK2,p-STAT3 and STAT3 in renal tissue of DHPK groups were significantly lower than those of model group(P<0.05),while the activity of SOD in renal tissue was significantly higher than that of model group(P<0.05).The pathological changes of kidney tissue were significantly improved.Conclusion:Rhubarb formula granule can significantly improve the renal function and oxidative stress damage of renal tissue in mice with gentamicin-induced renal injury,and its mechanism may be related to the regulation of JAK2/STAT3 signal pathway.