陈仲萍 林俊 王群

[摘要]目的 探讨TRPV5信号通路如何调控尿钙的重吸收，影响尿钙的浓度，从而影响到含钙肾结石的形成。方法 将20只SD大鼠随机抽取10只进入结石组，10只进入对照组。模型构建成功后，测定大鼠24 h尿钙浓度，并采用免疫组化和实时荧光定量PCR，分别检测TRPV5及其mRNA在大鼠肾脏中的表达情况。结果 结石组大鼠24 h尿钙浓度明显高于对照组大鼠，差异有统计学意义（P<0.01）；免疫组化显示结石组大鼠肾脏组织的TRPV5蛋白表达水平低于对照组，差异有统计学意义（P<0.01）；实时荧光定量PCR显示TRPV5mRNA表达量低于对照组，差异有统计学意义（P<0.01）。结论 TRPV5表达下降或缺乏可使肾小管对钙的重吸收减少，促进含钙肾结石的形成。

[关键词]TRPV5；尿钙；肾结石

[中图分类号] R277.514 [文献标识码] A [文章编号] 1674-4721（2018）9（a）-0008-04

[Abstract] Objective To discuss how the TRPV5 signaling pathway regulates the reabsorption of urinary calcium， thus affecting the concentration of urinary calcium and thereby affecting the formation of calcium-containing kidney stones. Methods The twenty SD rats were randomly selected to take ten into the stone group， the others into the control group. After the success of the model building， the determination of 24 hours urinary calcium concentration in rats， and the expression of TRPV5 and its mRNA in rat kidney were detected by immunohistochemical and quantitative real time PCR. Results It was found that urinary calcine concentration of 24 hour in the stone group was significantly higher than that in the control group， the difference was statistically significant （P<0.01）. The expression of TRPV5 protein and its mRNA in the stone group were lower than in the control group， the difference was statistically significant （P<0.01）. Conclusion The decrease of TRPV5 expression or lack of TRPV5 can reduce the reabsorption of calcium in renal tubules and promote the formation of calcium kidney stones.

[Key words] TRPV5； Urinary Calcium； Kidney Stone

泌尿系结石是泌尿系统的常见病、多发病，由多种因素共同作用所致，尿钙增高容易诱发或促进含钙尿路结石的形成。TRPV5是一种具有高度选择性的受体活化性离子通道，并受钙离子的反馈调节。其作为介导钙离子跨细胞膜轉运的通道，在调控尿钙水平中发挥关键作用，但其具体的调控机制仍不清楚。本研究通过研究TRPV5信号系统是否参与影响尿钙的重吸收，从而影响尿钙的浓度，进而影响到含钙肾结石的形成，为进一步防治含钙肾结石提供新的思路。

1材料与方法

1.1实验材料

1.1.1实验动物分组 SD大鼠20只，体重约150 g，购于福建医科大学实验动物中心[许可证号：SCXK（闽）2012-0001]。随机抽取10只大鼠进入结石组，10只进入对照组。

1.1.2动物模型构建 1%乙二醇配制：10 ml乙二醇加纯水定容至1000 ml；2%氯化氨配制：10 g氯化氨加纯水定容至500 ml。结石组大鼠每只每天给予1%乙二醇自由饮水，2%氯化氨灌胃2 ml/只。对照组给予正常水，余饲养条件相同，共饲养4周。喂养4周后，将大鼠放入代谢笼中收集24 h尿液后将大鼠处死，切取大鼠的一侧肾脏用10%福尔马林溶液固定，用于HE染色及免疫组化；……