摘要
目的:研究低分子量肝素(LMWH)对妊高征大鼠肾脏损伤的作用及其细胞内信号转导机制。方法:采用注射L NAME方法制备妊高征动物模型,将妊娠大鼠随机分为正常妊娠组、妊高征组、LMWH治疗组,测定各组平均动脉压、尿蛋白、血肌酐及血尿素氮,观察LMWH对肾脏各指标的影响及肾脏出现的病理学变化;同时采用免疫组化、RT PCR及WesternBlot方法检测ERK1/2在各组的表达变化。结果:LMWH治疗组肾脏组织ERK1/2的蛋白及mRNA表达水平明显低于妊高征组(P<0.01),而妊高征组肾脏组织ERK的蛋白及mRNA表达水平明显高于正常妊娠组(P<0.01),ERK1与ERK2在各组大鼠肾脏中的表达无差异;治疗组平均动脉压及尿蛋白明显低于非治疗组(P<0.05),但仍未达正常妊娠水平;HE染色和PAS染色为治疗组肾小球系膜增生、基底膜增厚较非治疗组明显减轻。ERK蛋白主要分布于肾小球中。结论:LMWH对妊高征大鼠肾脏损伤具有一定的防护作用,其机制可能是通过下调ERK1/2的表达来实现。
Aim: To investigate the protective effect of low molecular weight heparin(LMWH) on nephropathy in rats with pregnancy induced hypertension and to study its possible mechanism. Methods: The levels of the expression of renal ERK1/2 protein and mRNA were detected in PIH rats which were made by injection of L-NAME, normal pregnant rats and rats treated with LMWH by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction(RT-PCR). The renal tissue was observed by using light microscopy. Results: The expression level of renal ERK1/2 protein and mRNA in LMWH-treated rats were significantly lower than that in PIH rats, while the expression level of renal ERK1/2 protein and mRNA in PIH rats was significantly higher than that in normal pregnant rats(P<0.01), the intensity of ERK1/2 expression had no obvious differences among 3 groups. The average arterial pressure and urine protein in LMWH group were decreased, but no decrease was observed in normal rats. Mesangial expansion and basal membrane thickening were obviously retarded in LMWH- treated group. Conclusion: LMWH has renal protective effect on PIH rats, whose mechenism may be associated partly with a down-regulation of ERK expression.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2005年第2期212-215,i006,共5页
Chinese Journal of Applied Physiology
