Synaptopodin参与低分子肝素改善子痫前期大鼠蛋白尿的机制研究

Study the mechanism of low molecular weight heparin improving proteinuria of rats with L-NAME(NG-Nitro-L-arginine Methyl Ester) induced preeclampsia by regulation of synaptopodin

目的:探讨synaptopodin在低分子肝素(LMWH)治疗子痫前期(PE)大鼠模型中的分子作用机制。方法:将PE孕鼠随机分为3组:(1)L-NAME组:于妊娠第9天起连续腹腔内注射亚硝基左旋精氨酸甲酯(L-NAME)至孕期结束;(2)L-LMWH组:注射LNAME的同时,孕15天起连续腹腔内注射LMWH 200IU/(kg·d)至孕期结束;(3)H-LMWH组:注射L-NAME的同时,孕15天起连续腹腔内注射LMWH 600IU/(kg·d)至孕期结束。动态监测其血压、24h尿蛋白总量及胎鼠体重变化。采用荧光定量PCR方法、免疫组化法和Western blot法检测肾脏组织中synaptopodin表达。结果:H-LMWH组中synaptopodin表达明显高于L-NAME组(P<0.05),L-LMWH组和L-NAME组比较则无无明显变化(P>0.05)。孕17和19天时,与L-NAME组比较,H-LMWH组和L-LMWH组孕鼠的蛋白尿和血压均明显降低,差异有统计学意义(P<0.05);而胎鼠体重和胎鼠数无明显变化。结论:LMWH可能通过上调synaptopodin改善PE蛋白尿、降低血压。

Objective：To study the mechanism of low weight molecular heparin treating proteinuria of rats with L-NAME induced preeclampsia by synaptopodin. Methods：We dynami-cally monitored the blood pressure of tail artery,the total amount of 24h urinary protein and the mean body weight of pups of pregnancy rats after different concentration of low molecular weight heparin （ LMWH） administration. Meantime we detected synaptopodin expression of kidneys in pregnant rats after different concentration low molecular weight heparin （ LMWH ） administra-tion using RT-PCR, Immunohistochemical staining and Western blot. Results：Compared with the control,synaptopodin expression of kidneys in pregnant rats was significantly decreased after L-NAME injection. Synaptopodin expression of kidneys in pregnant rats was significantly in-creased after high concentration of LMWH （ H-LMWH ） administration compared with the L-NAME group. But synaptopodin expression had no changes between the L-NAME group and low concentration of LMWH （ L-LMWH） group. In addition,the blood pressure of tail artery and proteinuria of pregnant rats with L-NAME injection were markedly deceased after low and high concentration of LMWH administration [（200IU/（kg·d） and 600IU/（Kg·d）] on the 15th and 19th day. But the body weights of pups and the number of embryos per female did not change among the three groups. Conclusion：LMWH improved proteinuria of pregnant rats with L-NAME induced preeclampsia by up-regulation of synaptopodin,while LMWH improved pro-teinuria and decreased blood pressure of tail artery.