目的：观察中药清肾颗粒对肾间质纤维化（RIF）大鼠肾组织黏着斑激酶-Ras-丝裂素活化蛋白激酶（FAK-Ras-MAPK）信号转导通路的影响。方法将40只SD大鼠按随机数字表法分为正常对照组、模型组、百令胶囊组和清肾颗粒组，每组10只。采用单侧输尿管结扎（UUO）法制备RIF大鼠模型。术后百令胶囊组将百令胶囊溶于4 mL温水按0.3 g·kg-1·d-1灌胃；清肾颗粒组将清肾颗粒溶于4 mL温水按6 g·kg-1·d-1灌胃，正常对照组和模型组给予等量生理盐水灌胃。8周后检测各组大鼠血尿素氮（BUN）、肌酐（SCr）、纤维连接蛋白（FN）、α-肌动蛋白（α-SMA）水平；采用免疫组化法检测各组大鼠肾组织FAK、Ras、p38MAPK、FN、α-SMA的表达水平。结果模型组大鼠血清BUN、SCr、FN、α-SMA水平高于正常对照组；清肾颗粒组和百令胶囊组给药前血清BUN、SCr水平比较差异均无统计学意义（均P＞0.05）；给药后两组BUN、SCr、FN、α-SMA均较模型组显著降低，且以清肾颗粒组降低更显著〔BUN（mmol/L）：13.18±4.91比18.56±5.59，SCr （μmol/L）：104.80±12.04比119.02±12.47，FN（mg/L）：29.72±16.75比46.38±8.63，α-SMA（kU/L）：5.49±2.68比7.13±2.37，均P＜0.05〕；免疫组化结果显示：模型组大鼠肾脏组织中FAK、Ras、p38MAPK及FN、α-SMA表达均高于正常对照组，清肾颗粒组和百令胶囊组上述各指标表达均较模型组显著降低，且以清肾颗粒组的下降程度更显著（FAK：3.00±1.41比5.28±2.21，FN：4.25±1.04比6.29±2.06，α-SMA：3.25±1.28比4.86±1.57， p38MAPK：2.50±1.31比4.71±2.50，Ras：3.50±1.41比4.29±1.38，均P＜0.05）。结论清肾颗粒可以降低RIF大鼠血清BUN、SCr水平，抑制肾脏内FAK-Ras-MAPK信号转导通路的活化，从而减少FN和α-SMA生成，发挥抗RIF作用。%Objective To observe the effect of traditional Chinese medicine (TCM) Qingshen granule on signal transduction pathway of fokal adhesion kinase-rat sarcoma-mitogen activated protein kinase (FAK-Ras-MAPK) in renal tissue of rats with renal interstitial fibrosis (RIF). Methods Forty Spargue-Dawley (SD) rats were randomly divided into normal control, model, Bailing capsule and Qingshen granule groups (each, n = 10). The rat model with RIF was reproduced by unilateral ureteral obstruction (UUO) or ligation method. The rats in Bailing capsule group were treated with Bailing capsule dissolved in 4 mL warm water, and the dosage was 0.3 g·kg-1·d-1 for intragastric administration;the rats in Qingshen granule group were treated with Qingshen granule dissolved in 4 mL warm water, its dosage was 6 g·kg-1·d-1 for intragastric administration, and equal volume of normal saline was given to normal control group and model group by gavage. After treatment for 8 weeks, the levels of blood urea nitrogen (BUN), serum creatinine (SCr), fibronectin (FN),α-smooth muscle actin (α-SMA) were determined in each groups. The renal tissue expression levels of FAK, Ras, p38MAPK, FN, α-SMA were determined in various groups by immunohistochemistry staining method. Results Compared with the normal control group, the levels of serum BUN, SCr, FN and α-SMA were significantly increased in the model group. There were no significant differences in the levels of serum BUN and SCr before administration of drugs between Bailing capsule group and Qingshen granule group (both P>0.05). The levels of BUN, SCr, FN, andα-SMA were all significantly lowered in the two treatment groups than those of the model group after administration, the descent in Qingshen granule group being more marked [BUN (mmol/L):13.18±4.91 vs. 18.56±5.59, SCr (μmol/L): 104.80±12.04 vs. 119.02±12.47, FN (mg/L): 29.72±16.75 vs. 46.38±8.63, α-SMA (kU/L):5.49±2.68 vs. 7.13±2.37, all P < 0.05]. The immunohistochemistry staining showed: the kidney tissue expression levels of FAK, Ras, p38MAPK, FN, and α-SMA in the model group were significantly higher than those of normal control group, above indexes were all significantly lower in Bailing capsule group and Qingshen granule group than those of the model group, and the descent in Qingshen granule group was more obvious (FAK: 3.00±1.41 vs. 5.28±2.21, FN: 4.25±1.04 vs. 6.29±2.06, α-SMA: 3.25±1.28 vs. 4.86±1.57, p38MAPK: 2.50±1.31 vs. 4.71±2.50, Ras:3.50±1.41 vs. 4.29±1.38, all P<0.05). Conclusion Qingshen granule can reduce serum BUN and SCr levels in rats with RIF, and inhibit the activation of FAK-Ras-MAPK signal transduction pathway in the kidney, thereby it may reduce the generation of FN andα-SMA and play a role of anti-RIF.
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