替米沙坦对高脂饲养OLETF大鼠心肌重构及PPARγ表达的影响  

The effect of telmisartan on myocardial remodeling and expression of PPARγ in myocardial tissue in high-fat fed OLETF rats

作　　者：赵紫琴[1] 郑喜兰[2] 雒瑢[3] 田凤石[4] 方涛[4] 胡小宁 ZHAO Zi-qin;ZHENG Xi-lan;LUO Rong;TIAN feng-shi;FANG Tao(Department of Pathology, Tianjin Hospital, Tianjin, 300211, China;Department of Vasculocardiology, Tianjin Chest Hospital,30211,china;Department of Endocrinology, the Fourth Center Hospital of Tianjin,30211,china;Department of Vasculocardiology, Tianjin Haihe Hospital,30211,china)

机构地区：[1]天津市天津医院病理科,300211 [2]天津市海河医院心血管内科,30211 [3]天津市胸科医院内分泌科,300211 [4]天津市第四中心医院心血管内科,300211 [5]不详

出　　处：《天津医药》2018年第3期239-245,共7页Tianjin Medical Journal

基　　金：天津市应用基础与前沿技术研究计划青年项目资助(15JCQNJC13100)

摘　　要：目的探讨替米沙坦对高脂饲养的OLETF大鼠心肌重构及过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响。方法 4周龄雄性OLETF大鼠28只,高脂喂养。22周龄时称质量后随机分为替米沙坦组[O-T组,5mg/(kg·d),n=10],吡格列酮组[O-P组,10 mg/(kg·d),n=8]及无干预对照组[O-C组,等体积生理盐水,n=10],连续给药26周;选取性别、周龄匹配的正常非糖尿病LETO大鼠为空白对照(LETO组,n=12)。分别于22周龄和48周龄时行口服葡萄糖耐量试验(OGTT)检测大鼠2型糖尿病(T2DM)和糖耐量异常(IGT)发病情况。48周龄时给药结束后每组随机抽取5只大鼠行高胰岛素-正糖钳夹实验,计算60~120 min的葡萄糖输注速度(GIR60-120)。实验结束时处死动物,分离心脏,称量心脏质量(HW)和体质量(BW),以HW/BW判定心肌肥厚情况。ELISA法测定血清PPARγ、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平,放射免疫法测定血清脂联素水平。Real-time PCR检测心肌组织中PPARγ1、PPARγ2及IL-6 m RNA表达水平,Western blot法检测心肌组织中PPARγ、脂联素、IL-6及核因子(NF)-κB蛋白表达水平。光镜和电镜下分别观察各组大鼠心肌常规病理改变(HE染色、Masson染色、PAS染色)和超微结构改变。结果 22周龄时,各组大鼠均未发生T2DM及IGT。48周龄时O-C组7只发展为T2DM,2只IGT;O-T组1只T2DM,3只IGT;其他2组未见T2DM和IGT。48周龄时,O-P组、O-T组GIR60-120及HW/BW均明显低于O-C组(P<0.05),同时O-T组大鼠收缩压(SBP)、舒张压(DBP)较其他3组明显下降(P<0.05)。与O-C组相比,O-T组血清IL-6、TNF-α水平下降,脂联素和PPARγ水平则明显升高(P<0.05);O-P及O-T组间上述指标差异均无统计学意义。Real-time PCR及Westen blot结果显示,与O-C组相比,O-T组PPARγ1 m RNA表达升高、IL-6表达降低,O-P组及O-T组PPARγ、脂联素的蛋白表达均明显升高,而NF-κB及IL-6蛋白表达下降(均P<0.05)。光镜和电镜下可见O-C组心肌细胞受损严重,纤�Objective To investigate the effect of telmisartan on the expression of peroxisome proliferator activated receptor gamma(PPARγ)and its regulation in myocardial remodeling in spontaneously type2diabetic male Otsuka Long-Evans Tokushima Fatty(OLETF)rats fed with high-fat diet.Methods Twenty-eight four-week-old male OLETF rats were fed with high-fat diet.From22-week of age,the pre-diabetic OLETF rats were randomly assigned to three groups:telmisartan-treated group[O-T group,5mg/(kg·d),n=10],pioglitazone-treated group[O-P group,10mg/(kg·d),n=8]and untreated group(O-C group,equal volume of normal saline,n=10),continuously administration for22-week.Twelve sex and age matched Long-Evans Tokushima Otsuka(LETO)rats were used as control(LETO group).At22and48-week of age,the glucose tolerance of the rats was assessed by the oral glucose tolerance test(OGTT).At48weeks of age,five rats were randomly selected from each group,and clamp experiments were carried out.The glucose infusion rate from60min to120min(GIR60-120)was measured.All rats were sacrificed and the myocardial tissues were dissected.The ratio of heart weight to body weight(HW/BW)was calculated.Blood samples were collected,and serum PPARγ,tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and adiponectin were measured using ELISA and radioimmunoassay.The mRNA expressions of IL-6,PPARγ1and PPARγ2were measured by real-time PCR.The protein expression levels of PPARγ,adiponectin,IL-6and NF-κB were determined by Western blot assay.The myocardial pathological changes were observed under light microscope(HE staining,Masson staining and PAS staining),and ultrastructural changes were observed under transmission electron microscope.Results At22-week of age,neither type2diabetes mellitus(T2DM)nor IGT were found in three groups.At48-week of age,T2DM was found in seven rats of O-C group,and IGT was found in two rats.T2DM was found in one rat of O-C group,and IGT was found in three rats.Neither T2DM nor IGT was found in the other two groups.GIR60-120and HW/BW were al

关 键 词：大鼠 近交OLETF 心室重构 糖尿病 2型 过氧化物酶体增殖物激活受体Γ 替米沙坦 

分 类 号：R587.23[医药卫生—内分泌]