番石榴叶总黄酮对糖尿病大鼠肾脏Nrf2/HO-1信号通路的影响

Effects of TFPGL on Nrf2/HO-1 signaling pathway in kidneys of diabetic rats

目的探讨番石榴叶总黄酮(TFPGL)对糖尿病大鼠肾脏病变的保护作用及机制探讨。方法雄性SD大鼠24只,按随机数字表法分成对照组、糖尿病组、TFPGL治疗组,每组8只,后2组大鼠采用单次腹腔注射链脲佐菌素(55 mg/kg)诱导糖尿病模型,TFPGL治疗组加用200 mg/kg TFPGL灌胃。12周后收集血、尿及肾组织,检测血糖(BS)、血尿素氮(BUN)、尿蛋白/尿肌酐比值(ACR)及血清肌酐(SCr)的变化,HE染色检测肾脏病理改变,免疫荧光、免疫组织化学染色及Western blot检测肾脏核因子NF-E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)表达。结果与对照组相比,糖尿病组BS、BUN、ACR及SCr明显升高,Nrf2表达增加,HO-1表达下降(均P<0.05);而给予TFPGL治疗后,BS、BUN、ACR及SCr较糖尿病组明显降低,Nrf2、HO-1表达明显增加(均P<0.05)。结论 TFPGL对糖尿病大鼠肾脏病变具有一定的治疗效果,其机制可能与降低血糖和激活Nrf2/HO-1信号通路有关。

Objective To investigate the protective effect and mechanism of total flavones of psidium guajava leaves (TFPGL) on kidneys of diabetic rats. Methods Twenty-four male SD rats were divided into control group, diabetic group and TFPGL treatment group by random number table method. The diabetic model was induced by single intraperitoneal (IP) injection of streptozotocin (55 mg/kg). After 12 weeks, samples of blood, urine and kidney tissues were collected to detect the changes of blood sugar (BS), blood urea nitrogen (BUN), urine protein/creatinine ratio (ACR) and serum creatinine (SCr). The pathological changes of kidney were detected by HE staining. The expressions of Nrf2 and HO-1 in kidney were detected by immunofluorescence, immunohistochemical staining and Western blot assay. Results Compared with the control group, BS, BUN, ACR and SCr were increased significantly in diabetic group, the expression of Nrf2 was increased, the expression of HO-1 was decreased (all P<0.01). Compared with the diabetic group, the levels of BS, BUN, ACR and SCr were decreased significantly, while Nrf2 and HO-1 increased significantly in diabetic group after treatment with TFPGL (all P<0.05). Conclusion TFPGL has a certain therapeutic effect on diabetic nephropathy in rats. Its mechanism may be related to the decreased blood sugar and activated Nrf2/HO-1 signaling pathway.