厄贝沙坦对糖尿病胃轻瘫大鼠ET-1和AT1R表达的影响  

Effect of irbesartan on expression of ET-1 and AT1R in gastric tissues of diabetic rats with gastroparesis

作　　者：何莉莉[1] 朱雅娜[1] 任荣[1] 张玉[1] 王飞[1] 李媛[1] 张艺凡[2] 孙玉凤[3] 

机构地区：[1]河北医科大学第二医院消化内科河北省消化病重点实验室,河北省石家庄市050000 [2]河北省石家庄市中心医院中西医结合内科,河北省石家庄市050000 [3]河北医科大学第二医院消化内科 河北省消化病重点实验室,河北省石家庄市050000

出　　处：《世界华人消化杂志》2013年第9期798-803,共6页World Chinese Journal of Digestology

摘　　要：目的:研究厄贝沙坦对糖尿病胃轻瘫(diabetic gastroparesis,DG)的治疗作用及其可能的作用机制.方法:30只健康♂SD大鼠予链脲佐菌素(streptozotocin,STZ)腹腔注射,制备糖尿病大鼠模型.随机分为正常对照组(NC组)、糖尿病模型对照组(DC组)、厄贝沙坦治疗组(DI组),DI组予以厄贝沙坦按0.012g/(kgd)灌胃,其余两组给予等体积生理盐水灌胃.6wk后,行酚红灌胃法测胃排空率;放射免疫分析法测定大鼠胃组织内皮素(ET-1)含量、化学比色法检测胃组织一氧化氮合酶(NOS)活性、反转录聚合酶联反应(RT-PCR)测定胃组织血管紧张素受体(AT1R)mRNA表达.结果:DC组及DI组的胃排空率较NC组明显下降(18.65%±4.30%,22.64%±2.88% vs 62.64%±4.51%),而与DC组相比,DI组的胃排空率明显升高(22.64%±2.88%vs18.65%±4.30%;DI组胃组织ET-1含量较DC组明显下降(21.660pg/mgpro±4.686pg/mgpro vs 26.850pg/mgpro±2.897pg/mgpro),但是仍高于NC组(21.660pg/mgpro±4.686pg/mgpro vs 18.520pg/mgpro±2.795pg/mgpro);NOS分为结构性NOS(cNOS)和诱导性(iNOS),与NC组相比,DC组、DI组cNOS活性显著下降(0.521pg/mgpro±0.057pg/mgpro vs 0.323pg/mgpro±0.079pg/mgpro,0.384pg/mgpro±0.067pg/mgpro),DI组cNOS活性较之DC组没有显著差异(0.323pg/mgpro±0.079pg/mgpro vs 0.384pg/mgpro±0.067pg/mgpro),而DI组iNOS活性较DC组明显下降(0.246pg/mgpro±0.033pg/mgpro vs 0.276pg/mgpro±0.021pg/mgpro),但仍高于NC组(0.246pg/mgpro±0.033pg/mgpro vs 0.209pg/mgpro±0.015pg/mgpro);厄贝沙坦干预后,DI组胃组织(AT1R)mRNA表达低于DC组,差异有统计学意义(0.546±0.005 vs 0.741±0.010),而仍显著高于NC组(0.546±0.005 vs 0.207±0.004).结论:厄贝沙坦可能通过影响DG大鼠胃组织ET-1、NOS、AT1RmRNA水平来改善DG大鼠的胃排空障碍.AIM： To investigate the therapeutical effect of irbesartan on diabetic gastroparesis （DG） in rats and to explore potential mechanisms involved. METHODS： Thirty male Sprague-Dawley rats were randomly divided into either a normal control group （NC group, n=10） or a diabetes mellitus group （DM group, n=20）. Diabetes mellitus was induced with streptozotocin （50 mg/kg i.p.）. The DM group was further divided into a diabetic control group （DC group, n=10）and an irbesartan group （DI group, n = 10）. The DI group was given irbesartan 0.012 g/（kg d） through stomach feeding, while the NC and DC groups were given equal volume of saline by gavage. Six weeks later, all the rats were admin-istered with phenol red solution to measure the rate of gastric emptying. Endothelin （ET-1） content in stomach tissue was measured by radio-immunoassay. Chemical colorimetry was used to measure the activity of nitric oxide synthase （NOS） in the stomach tissue. The expression level of angiotensin receptor （AT1R） mRNA was determined by RT-PCR. RESULTS： Compared to the NC group, the rate of gastric emptying significantly decline in the other two groups （62.64% ± 4.51% vs 18.65% ± 4.30%, 22.64% ± 2.88%）; however, the rate of gastric emptying was significantly higher in the DI group than in the DC group （22.64% ± 2.88% vs 18.65% ± 4.30%）. There was a significant difference in ET-1 content among the three groups （NC 18.520 pg/mgpro ± 2.795 pg/mgpro vs DC 26.850 pg/mgpro ± 2.897 pg/mgpro vs DI 21.660 pg/mgpro ± 4.686 pg/mgpro）. Compared to the NC group, cNOS activity significantly declined in the DC and DI groups （0.521 pg/mgpro ± 0.057 pg/mgpro vs 0.323 pg/mgpro ± 0.079 pg/mg-pro, 0.384 pg/mgpro ± 0.067 pg/mgpro）; however, there was no significant change in cNOS activity between the DC and DI groups （0.323 pg/mgpro ± 0.079 pg/mgpro vs 0.384 pg/mg-pro ± 0.067 pg/mgpro）. iNOS activity in the DI group was significantly lower than that in the DC group （0.246 pg/mgpro ± 0.0

关 键 词：糖尿病 胃轻瘫 厄贝沙坦 胃排空率 内皮素 一氧化氮合酶 血管紧张素受体 

分 类 号：R587.2[医药卫生—内分泌]