左卡尼汀通过TGF-β_(1)/Smad通路对尿毒症腹膜透析大鼠钙磷代谢的影响

Effect of L-carnitine on calcium and phosphorus metabolism in uremic peritoneal dialysis rats through TGF-β_(1)/smad pathway

目的探讨左卡尼汀通过转化生长因子-β_(1)/Sma和Mad相关蛋白(TGF-β_(1)/Smad)信号通路对尿毒症腹膜透析大鼠钙磷代谢的影响。方法将尿毒症腹膜透析大鼠分为模型组和左卡尼汀组,另给予假手术的大鼠作为对照组,每组10只。模型组和对照组分别灌胃生理盐水,左卡尼汀组灌胃左卡尼汀40 mg/kg,1次/d,持续6周。采用酶联免疫吸附试验(ELISA)检测血尿素氮、肌酐、甲状旁腺激素及钙、磷水平。采用Western blotting检测肾组织TGF-β_(1)、Smad及磷酸化Smad3(p-Smad3)蛋白相对表达量。结果模型复制前3组大鼠体重比较,差异无统计学意义(P>0.05)。模型复制6周后,与对照组比较,模型组和左卡尼汀组大鼠血肌酐、尿素氮、甲状旁腺激素及磷水平均升高(P<0.05),血钙水平降低(P<0.05),与模型组比较,左卡尼汀组大鼠血肌酐、尿素氮、甲状旁腺激素及磷水平均降低(P<0.05),血钙水平升高(P<0.05)。与对照组比较,模型组和左卡尼汀组大鼠TGF-β_(1)和p-Smad3蛋白相对表达量均上调(P<0.05),与模型组比较,左卡尼汀组大鼠TGF-β_(1)和p-Smad3蛋白表达水平均下调(P<0.05)。结论左卡尼汀可通过抑制尿毒症腹膜透析的TGF-β_(1)/Smad通路活化来改善肾脏功能,提高血甲状旁腺激素、钙、磷水平,改善钙磷代谢平衡。

Objective To investigate the effect of L-carnitine on transforming growth factor-β_(1)(TGF-β_(1))/Sma and Mad related protein(Smad) signaling pathway and calcium and phosphorus metabolism in uremic peritoneal dialysis rats. Methods The rats were divided into 3 groups: the sham operation group, the model group and the left carnitine group. Each group was given medicine or saline once a day for 6 weeks. The levels of urea nitrogen, creatinine, parathyroid hormone, calcium and phosphorus were measured by enzyme-linked immunosorbent assay(ELISA). The expression of transforming growth factor-β_(1)(TGF-β_(1)), Sma-and Mad-related protein(Smad) and phosphorylation of Smad(p-Smad3) in renal tissue was detected by Western blotting. Results There was no significant difference in body weight among 3 groups before modeling. After 6 weeks of modeling,compared with the sham operation group, the serum creatinine, urea nitrogen, parathyroid hormone and phosphorus water in the model group and the left carnitine group increased significantly, the serum calcium level decreased significantly, and the expression levels of TGF-β_(1)and p-smad3 protein increased significantly(all P < 0.05).Compared with the model group, the level of serum calcium, serum creatinine, urea nitrogen, serum phosphorus and parathyroid hormone were significantly increased. The expression of TGF-β_(1)and p-smad3 protein was significantly decreased in the L-carnitine group(all P < 0.05). Conclusion By inhibiting the activation of the uremic peritoneal dialysis TGF-β_(1)/Smad pathway, L-carnitine can improve renal function, increase the levels of serum calcium,phosphorus and parathyroid hormone, so as to achieve the balance of calcium and phosphorus metabolism in uremic peritoneal dialysis.