排石汤对肾结石模型大鼠保护作用及机制研究

Protection and mechanism of Paishi Decoction on nephrolith model rats

关键词:  排石汤  肾结石  炎症因子  转化生长因子-β1  p38 MAPK

Key words:  Pashi Decotion  renal calculi  inflammatory factor  TGF-β1  p38 MAPK

摘要:

[目的] 观察排石汤对肾结石模型大鼠肾功能的保护作用，并初步探讨其机制。[方法] 采用1%乙二醇和2%氯化铵溶液灌胃建立肾结石大鼠模型，将40只健康雄性SD大鼠随机分为正常组、模型组、枸橼酸钾组和排石汤低、高剂量组，每组8只。给药4周，检测24 h尿量、肾脏系数、血清尿素氮(BUN)、肌酐(Scr)等生化指标，苏木精-伊红(HE)染色检测肾损伤，酶联免疫吸附(ELISA)法检测炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)及白细胞介素-1β(IL-1β)，免疫组化法测定转化生长因子-β1(TGF-β1)，Western blot法测定丝裂原活化蛋白激酶(p38 MAPK)。[结果] 与模型组比较，排石汤高、低剂量组24 h尿量明显增加(P＜0．01)，肾脏系数明显降低(P＜0．01)，肾损伤程度较轻。与模型组比较，排石汤高、低剂量组BUN和Scr水平明显降低(P＜0．01)。与模型组相比，排石汤高、低剂量组TNF-α、IL-6和IL-1β指标显著降低(P＜0．01)。与模型组比较，排石汤高、低剂量组TGF-β1/p38 MAPK水平显著低于模型组(P＜0．01)。[结论] 排石汤能抑制草酸钙结石形成，改善大鼠肾脏功能，降低血中炎症细胞因子水平，抑制TGF-β1/p38 MAPK信号通路，进而发挥肾脏保护作用。

Abstract:

[Objective] To investigate the effect of Paishi Decoction on nephrolith model rats,and explore its mechanism preliminarily. [Methods] Forty healthy male SD rats were divided randomly into normal group,model group,potassium citrate solution group and low,high dose Paishi Decoction group,8 rats in each groups,built nephrolith rat model by intragastricly administrated 1% ethylene glycol(EG),together with 2% ammonium chloride(AC). After 4 weeks treatment,the 24 h urine output,renal coefficent and serum BUN,Scr were observed,renal pathological changes were observed with hematoxylin-eosin staining,plasma concentrations of TNF-α,IL-6 and IL-1β were detected by ELISA,the expression of TGF-β1 was detected by Immunohistochemistry and the expression of p38MAPK by Western blot. [Results] Compared with the model group,the 24 h urine output of the high and low dose Paishi Decoction group significantly increased(P<0.01),and the renal coefficient decreased significantly(P<0.01),while the degree of renal injury was reduced. Compared with the model group,the concentrations of BUN and Scr in the high and low dose Paishi Decoction group were decreased significantly(P<0.01). Compared with the model group,the concentrations of TNF-α,IL-6 and IL-1β in the high and low dose Paishi Decoction group were significantly decreased(P<0.01). Compared with the model group,the protein expression of TGF-β1 and p38 MAPK in the high and low dose Paishi Decoction group decreased significantly(P<0.01). [Conclusion] Paishi Decoction can inhibit the formation of renal calcium oxalate crystal,improve renal function in rats,reduce levels of inflammatory cytokines and inhibit the TGF-β1 and p38 MAPK signaling pathway,and finally play a role in protecting renal function.