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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 investigate the molecular mechanism of synaptopodin in the treatment of preeclampsia (PE) rats with low molecular weight heparin (LMWH). Methods: Pregnant PE rats were randomly divided into 3 groups: (1) L-NAME group: continuous intraperitoneal injection of L-NAME on the 9th day of gestation until the end of pregnancy; (2) ) L-LMWH group: intraperitoneal injection of LMWH 200 IU / (kg · d) intraperitoneally from the 15th day of pregnancy to the end of pregnancy at the same time of injecting LNAME; (3) H-LMWH group: injected with L-NAME Continuous intraperitoneal injection of LMWH 600IU / (kg · d) until the end of pregnancy. Dynamic monitoring of blood pressure, 24h urinary protein and fetal rat body weight changes. The expression of synaptopodin in renal tissues was detected by fluorescence quantitative PCR, immunohistochemistry and Western blot. Results: The expression of synaptopodin in H-LMWH group was significantly higher than that in L-NAME group (P <0.05). There was no significant difference between L-LMWH group and L-NAME group (P> 0.05). Compared with L-NAME group, the proteinuria and blood pressure of pregnant rats in H-LMWH group and L-LMWH group were significantly lower than those in L-NAME group on the 17th and 19th day of pregnancy, the difference was statistically significant (P <0.05) No significant change in the number of rats. Conclusion: LMWH may improve PE proteinuria and lower blood pressure by up-regulating synaptopodin.