目的 探讨肾脏DNA甲基转移酶(DNMTs)在孕期脂多糖(LPS)刺激仔鼠高血压发生的作用。方法 将孕鼠分为4组,分别为对照组(孕期的8~14d注射生理盐水)、LPS组(孕期第8、10、12天注射LPS,在9、11、13、14天注射生理盐水)、核转录因子κB(NF-κB)抑制剂PDTC组(孕期的8~14d每天注射PDTC)、LPS+PDTC组(LPS在孕期第8、10、12天注射,PDTC注射时间及剂量同PDTC组)。用尾动脉无创血压测定仪测仔鼠血压,电子天平称体质量,RT-PCR检测仔鼠肾皮质白细胞介素-6(IL-6)、Fli-1及DNMTs的表达水平。结果LPS组仔鼠血压明显高于对照组(P〈0.05),体质量较对照组高,肾皮质IL-6、Fli-1、DNMT1、DNMT3b表达较对照组升高(P〈0.05)。而LPS+PDTC组仔鼠体质量、血压及IL-6、Fli-1、DNMT1、DNMT3b表达均较LPS组降低。结论 孕期LPS刺激会引起仔鼠肾皮质DNA甲基酶变化,提示一些关键基因的甲基化可能是孕期LPS刺激引起子代高血压的原因之一。
Objective To investigate the role of renal DNA methyltransferases (DNMTs) stimulated by lipopolysaccharide (LPS) during gestational period in the hypertension occurrence in offspring rat. Methods Pregnant rats were randomly divided into four group (n~ 8 each) ..control group (injection of normal saline on 8--14 d of gestation) ;LPS group (injection of LPS on 8,10,12 d of pregnancy and injection of normal saline on 9,11,13,14 d), NF-κB inhibitor PDTC group (injection of PDTC on 8 -14 d of gestation) ,LPS+PDTC group (injection of LPS on 8,10,12 d of gestation,PDTC dose and injection time same to PDTC group). The tail noninvasive blood pressure determinator was adopted to detect the offspring blood pressure. The body weight was weighed by the electronic balance. The expression levels of IL-6, Fli-land DNMTs in offspring renal cortex were detected by RT-PCR. Re- suits The blood pressure in the LPS group was significantly higher than that in the control group and the body weight was higher than that in the control group(P〈0.05). The expression levels of IL-6, Fli-1,DNMT1 and DNMT3b in the renal cortex were increased compared with the control group(P〈0.05). But the body weight,blood pressure and expression levels of IL-6,Fli-1,DN- MT1 and DNMT3b in the LPS+PDTC group were decreased compared with the LPS group. Conclusion The LPS stimulation during gestational period could resulted in the change of intrarenal DNMTs in offspring rats, prompting that the methylation of some key genes could be one of the reasons for LPS stimulation during gestational period causing hypertension in offspring.