丝裂原活化的蛋白激酶p38在健脾清化方改善大鼠慢性肾衰竭中的意义

MAPK p38 pathway may be involved in renal function improvement in chronic renal failure rats treated with Jianpi Qinghua Decoction

目的:探讨丝裂原活化蛋白激酶(MAPK)p38在健脾清化方改善模型大鼠慢性肾衰竭肾纤维化中的作用。方法:SPF级SD大鼠分为假手术组(n=10)、模型组(n=10)、健脾清化方组(n=10)、氯沙坦组(n=10)。健脾清化方组每日灌胃1次,每次3.9 g/200 g大鼠,连续60 d;氯沙坦组每日灌胃1次,每次3.3 g/200 g大鼠,连续60 d;假手术组和模型组等体积生理盐水灌胃。5/6肾切除大鼠模型(Platt法),采用生化法检测大鼠血清肌酐、尿素氮,蛋白质印迹法检测MAPK p38,HE染色观察肾脏组织病理学变化。结果:与模型组比较,健脾清化方、氯沙坦能显著降低血清肌酐水平(42.67±5.98 vs 60.90±9.54,40.90±5.07 vs 60.90±9.54,均P<0.01)及MAPK p38表达(0.555±0.004 vs 0.930±0.265,0.587±0.045 vs 0.930±0.265,均P<0.01),降低大鼠血清尿素氮水平(8.56±0.75 vs 8.62±0.62,7.97±0.86 vs 8.62±0.62,均P<0.05);模型组可见肾小球增生,系膜细胞轻度增生,间质炎性细胞浸润,健脾清化方组、氯沙坦组与模型组比较病变明显减轻,且健脾清化方组较氯沙坦组病变减轻更明显。结论:健脾清化方对Platt模型大鼠的肾功能和肾脏病理有一定的改善作用,该机制可能与健脾清化方对MAPK p38相关免疫炎症通路的抑制有关。

Objective：To investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats.Methods：Forty SPF SD rats were divided into sham group（n =10）,model group（n =10）,Jianpi Qinghua group（n =10） and losartan group（n =10）.Rat chronic renal failure was induced by 5/6 nephrectomy （Platt method） in model,Jianpi Qinghua and losartan groups,and rats in sham group received sham operation.Jianpi Qinghua decoction （3.9 g · 200g-1） or losartan （3.3 g · 200 g-1） daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days,respectively.Rats in sham and model groups were orally administered with saline of the same volume.The serum levels of creatinine and urea nitrogen were measured by biochemical method,the expression of MAPK p38 was detected by Western Blot,and renal pathological changes were observed with hematoxylin-eosin staining.Results：Compared to model group,serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly （42.67 ± 5.98 or 40.90 ±5.07 vs 60.90 ± 9.54,both P ＜ 0.01）,the expression of MAPK p38 was significandy down-regulated （0.555 ±0.004 or 0.587 ±0.045 vs 0.930 ±0.265,both P ＜0.01） and serum urea nitrogen was also decreased （8.56 ± 0.75 or 7.97 ± 0.86 vs 8.62 ± 0.62,both P ＜ 0.05）.The renal pathology in the model group presented glomerular mesangial proliferation,hyperplasia of glomenrulus mesangial cells and interstitial inflammation.Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups.Conclusion：Jianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure,which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.