氯沙坦调节TLR4/NF-κB信号通路对肾血管性高血压大鼠左心室重构的保护作用  

Protective effect of losartan on left ventricular remodeling in renal vascular hypertension rats by regulating TLR4/NF-κB signaling pathway

作　　者：陈强[1] 菅建国[1] 张娟[1] 陈丽珠[1] CHEN Qiang;JIAN Jianguo;ZHANG Juan;CHEN Lizhu(Internal Medicine-Cardiovascular Department,the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014010,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院心内科,包头014010

出　　处：《中国免疫学杂志》2022年第2期154-159,共6页Chinese Journal of Immunology

基　　金：包头医学院科学研究基金项目(BYJJ-QM-2018016);内蒙古自治区高等学校科学研究项目(NJZY19190)。

摘　　要：目的:探讨氯沙坦对肾血管性高血压大鼠左心室重构的干预机制。方法:将45只SD大鼠随机分为3组,空白对照组(Sham)、模型对照组(RVH)和氯沙坦(LOS)干预组(RVH+LOS),每组各15只。模型对照组和干预组用"双肾双夹"方法构建大鼠肾血管性高血压(RVH)模型,干预组每天给予氯沙坦(5、10、20 mg∕kg)灌胃治疗,空白对照组和模型对照组给予等量生理盐水灌胃,连续治疗4周。结束后用彩色多普勒超声波诊断仪评价心功能;记录大鼠体质量后处死大鼠,取出心脏,分别称量各组大鼠的心脏(HW)、心室(VW)和左心室重量(LVW),并计算左心室/体质量指数(LVW/BW);Masson染色评估各组大鼠心肌胶原容积分数(CVF);ELISA平行测定各组大鼠血浆中CRP、TNF-α、IL-1、IL-6、IL-10含量水平;免疫组化检测心肌组织TLR4及NF-κB的表达情况。结果:与Sham组相比,RVH组左室舒张末期内径(LVEDD)及收缩末期内径(LVESD)显著增加(P<0.05),左室短轴缩短率(LVFS)和射血分数(EF)显著降低(P<0.05);与RVH组相比,RVH+LOS组LVEDD、LVESD明显降低(P<0.05),LVFS和EF明显升高(P<0.05)。RVH组HW、VW、LVW和LVW/BW均大于Sham组和RVH+LOS组。Masson染色结果显示,RVH组心肌胶原容积分数CVF也明显高于Sham组和RVH+LOS组(P<0.05)。ELISA结果显示,RVH组大鼠血浆中CRP、TNF-α、IL-6含量明显高于Sham组和RVH+LOS组(P<0.05),IL-10含量明显低于Sham组和RVH+LOS组(P<0.05)。RVH组大鼠心肌组织中TLR4及NF-κB的蛋白表达明显高于Sham组和RVH+LOS组(P<0.05)。结论:肾血管性高血压大鼠通过激活TLR4/NF-κB通路引起心室增大,心功能受损等左心室重构表现,氯沙坦干预治疗通过抑制TLR4/NF-κB通路明显改善高血压引起的左心室重构。Objective:To investigate the intervention mechanism of losartan on left ventricular remodeling in renal vascular hypertension rats.Methods:45 SD rats were randomly divided into three groups,the blank control group(Sham),the model control group(RVH)and the losartan(LOS)intervention group(RVH+LOS),with 15 rats in each group. Renal vascular hypertension(RVH)model was established in the model control group and the intervention group by "double-kidney double-clamp" method. The intervention group was given losartan(5,10,20 mg/kg)by gavage every day,while the blank control group and the model control group were given the same amount of normal saline by gavage,and the treatment was continued for 4 weeks. After the end,the cardiac function was evaluated by color doppler ultrasound. After recorded the weight,killed the rats and taken out the heart,the hearts(HW),ventricles(VW)and left ventricle weights(LVW)of each group were measured,and the left ventricle/body mass index(LVW/BW)was calculated. The myocardial collagen volume fraction(CVF)of each group was evaluated by Masson staining. The levels of plasma CRP,TNF-α,IL-1,IL-6 and IL-10 were detected by ELISA. The expression of TLR4 and NF-κB in myocardial tissue was detected by immunohistochemistry.Results:Compared with Sham group,left ventricular end diastolic diameter(LVEDD)and end systolic diameter(LVESD)in RVH group were significantly increased(P<0.05),left ventricular short axis shortening rate(LVFS)and ejection fraction(EF)were significantly decreased(P<0.05);compared with RVH group,LVEDD and LVESD in RVH+LOS group were significantly decreased(P<0.05),and LVFS and EF were significantly increased(P<0.05). HW,VW,LVW and LVW/BW in RVH group were higher than Sham group and RVH+LOS group. Masson staining results showed that the myocardial collagen volume fraction of CVF in RVH group was also significantly higher than that in Sham group and RVH+LOS group(P<0.05).ELISA results showed that the levels of plasma CRP,TNF-α and IL-6 of rats in RVH group were significantly high

关 键 词：肾血管性高血压 左心室重构 氯沙坦 TLR4/NF-κB信号通路 

分 类 号：R544[医药卫生—心血管疾病]