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康仙灵汤对单侧输尿管梗阻大鼠肾组织肝细胞生长因子mRNA表达及细胞外信号调节蛋白激酶1/2和p38磷酸化的影响

[Effect of Kangxianling Decoction on expression of hepatocyte growth factor mRNA and phosphorylations of extracellular signal-regulated protein kinase 1/2 and p38 in renal tissue of rats with unilateral ureteral obstruction].

作者信息

Zhang Yue, Liu Yu-min, Lu Hai-ying, Liu Ke-jian, Li Jing, He Li-qun, Lin Min, Zhou Li

机构信息

Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Zhong Xi Yi Jie He Xue Bao. 2007 Nov;5(6):656-60. doi: 10.3736/jcim20070611.

Abstract

OBJECTIVE

To study the effect of Kangxianling Decoction (KXLD), a compound traditional Chinese herbal medicine, on expression of hepatocyte growth factor (HGF) mRNA and phosphorylations of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 in renal tissue of rats with unilateral ureteral obstruction (UUO).

METHODS

Eighteen male SD rats were randomly divided into 3 groups: sham-operated group, untreated group and KXLD-treated group. A rat model of renal interstitial fibrosis was established by UUO. Rats with UUO were sacrificed after intragastric administration of KXLD for 14 days, and the parameters such as serum creatinine (SCr), blood urea nitrogen (BUN) and hydroxyproline in the kidney of rats in 3 groups were analyzed. The expression of HGF mRNA in kidney tissue was determined by reverse transcription polymerase chain reaction. The expressions of c-Met protein, ERK1/2 protein, p38 protein and the phosphorylations of ERK1/2 and p38 were determined by Western blotting method.

RESULTS

The levels of SCr, BUN and hydroxyproline in the untreated group were significantly increased as compared with those in the sham-operated group (P<0.05). The expression of HGF mRNA in the untreated group was significantly down-regulated. The expression of c-Met protein and the phosphorylations of ERK1/2 and p38 in the kidney tissue of rats with UUO in the untreated group were significantly up-regulated. After intervention with KXLD, the phosphorylations of ERK1/2 and p38 were all significantly inhibited except for c-Met expression. The HGF mRNA was increased in KXLD-treated group.

CONCLUSION

KXLD can decrease the level of collagen in the obstructed kidney of rats with UUO and alleviate the renal interstitial fibrosis in rats with UUO through enhancing the HGF mRNA expression and inhibiting the phosphorylations of ERK1/2 and p38.

摘要

目的

研究复方中药抗纤灵汤(KXLD)对单侧输尿管梗阻(UUO)大鼠肾组织中肝细胞生长因子(HGF)mRNA表达及细胞外信号调节蛋白激酶1/2(ERK 1/2)和p38磷酸化的影响。

方法

将18只雄性SD大鼠随机分为3组:假手术组、未治疗组和KXLD治疗组。通过UUO建立大鼠肾间质纤维化模型。UUO大鼠在灌胃给予KXLD 14天后处死,分析3组大鼠血清肌酐(SCr)、血尿素氮(BUN)及肾脏羟脯氨酸等参数。采用逆转录聚合酶链反应测定肾组织中HGF mRNA的表达。采用蛋白质印迹法测定c-Met蛋白、ERK1/2蛋白、p38蛋白的表达及ERK1/2和p38的磷酸化水平。

结果

与假手术组相比,未治疗组的SCr、BUN和羟脯氨酸水平显著升高(P<0.05)。未治疗组HGF mRNA表达显著下调。未治疗组UUO大鼠肾组织中c-Met蛋白表达及ERK1/2和p38磷酸化均显著上调。KXLD干预后,除c-Met表达外,ERK1/2和p38的磷酸化均显著受到抑制。KXLD治疗组HGF mRNA增加。

结论

KXLD可降低UUO大鼠梗阻肾脏的胶原水平,通过增强HGF mRNA表达及抑制ERK1/2和p38的磷酸化来减轻UUO大鼠的肾间质纤维化。

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