禾肾丸对阿霉素肾病大鼠肾脏podocalyxin及α-actinin-4蛋白表达的影响

Effects of Heshen pills on renal expression of podocalyxin and α-actinin-4 in rats with adriamycin nephropathy

目的:观察禾肾丸对阿霉素肾病大鼠肾脏podocalyxin及α-actinin-4蛋白表达的影响,探讨禾肾丸减少尿蛋白的可能机制。方法:将80只SPF级SD雄性大鼠随机分为正常组、模型组、依那普利组和禾肾丸组。一次性尾静脉注射阿霉素造模并予药物干预,第2、4、6、8周留取24h尿标本,观察24h尿蛋白定量,取肾组织观察大鼠肾脏组织形态学的变化,检测大鼠肾脏的podocalyxin及α-actinin-4蛋白表达情况。结果:依那普利组、禾肾丸组、模型组24h尿蛋白定量较正常组明显增高(P<0.05),肾脏病理损伤明显,podocalyxin蛋白表达量减少、α-actinin-4蛋白表达量无明显变化但异常分布明显;与模型组比较,依那普利组、禾肾丸组治疗第8周24h,尿蛋白定量明显减少(P<0.05)、肾脏病理损伤明显减轻、大鼠肾脏podocalyxin表达明显高于同期模型组(P<0.05),α-actinin-4的表达量较同期模型组无明显差异,但异常分布较模型组为轻。结论:禾肾丸能减少阿霉素肾病大鼠24h尿蛋白、减轻阿霉素肾病大鼠肾脏病理损伤,其作用机制与其上调阿霉素肾病大鼠肾脏podocalyxin表达、减轻α-actinin-4的异常分布有关。

Objective： To observe the effects of Heshen pills on the renal expression of podocalyxin and α- actinin- 4 in rats with adriamycin nephropathy,and to investigate the possible mechanism of action of Heshen pills in reducing urinary protein. Methods： Eighty specific pathogen- free Sprague- Dawley rats were randomly divided into normal group,model group,enalapril group,and Heshen pill group. The rat model was established by a single tailvein injection of adriamycin and then treated with drugs. At 2,4,6,and 8 weeks after gavage,24- h urinary samples were collected and 24- h urinary protein was determined quantitatively. Rats were sacrificed at 2,4,6,and 8 weeks after treatment,and renal tissue was collected for observation of histomorphological changes and determination of expression of podocalyxin and α- actinin- 4 in rat kidney. Results： Compared with the normal group,the model group had a significantly higher level of 24- h urinary protein,significant pathological injury in the kidney,and significantly lower expression of podocalyxin at different time points（ P〈 0. 01）. There was no substantial difference in expression of α- actinin- 4 between the normal group and the model group. However,abnormal distribution of α-actinin- 4 was found in the model group. Compared with rats in the model group,rats treated with enalapril or Heshen pills had a significantly lower level of 24- h urinary protein at 8 weeks after gavage（ P 〈0. 05）,mitigated pathological injury in the kidney,and significantly higher expression of podocalyxin at different time points（ P 〈0. 05）. There was no substantial difference in expression of α- actinin- 4 at each time point between rats in the model group and rats treated with enalapril or Heshen pills. However,the abnormal distribution of α- actinin- 4 was milder in rats treated with enalapril or Heshen pills compared with rats in the model group. Conclusion： Heshen pills can reduce 24- h urinary protein and resolve pathological injury in the kidney of rats with adriamycin nephropathy,probably by upregulating the renal expression of podocalyxin and mitigating the abnormal distribution of α- actinin- 4.