摘要
目的探讨瑞舒伐他汀对急性心肌梗死(AMI)大鼠心肌细胞保护作用及Rho A/ROCK活化机制。方法选取生理状况相近的SD大鼠40只,并按照随机数字表法将其分为瑞舒伐他汀组、AMI组、假手术组、正常组四组,平均每组10只;使用ELISA法对白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)等水平进行检测;使用试剂盒法对各组大鼠肌酸激酶(CK)和丙二醛(MDA)、超氧化物转化酶(SOD)以及乳酸脱氢酶(LDH)的表达水平进行检测;利用HE染色对大鼠心脏组织病理变化进行检测,使用TUNEL法检测大鼠心肌细胞凋亡情况;使用TTC/伊文思蓝染色测定大鼠的心肌相应梗死面积;使用Western印迹法检测大鼠体内NF-κBp65、ROCK1、ROCK2、Bcl-2、Bax等表达水平。结果瑞舒伐他汀组大鼠梗死面积下降至(30.00±7.00)%,显著低于AMI组大鼠心肌梗死面积(43.00±5.00)%(P<0.05);且瑞舒伐他汀组大鼠血清中心肌损伤标记分子LDH和CK水平均显著低于AMI组大鼠(均P<0.05)。AMI组大鼠心肌组织和血清中的抗氧化分子SOD水平较假手术组大鼠急剧下降,同时AMI组大鼠氧化损伤标致分子MDA水平则显著高于假手术组大鼠(均P<0.01);而瑞舒伐他汀组大鼠MDA水平则显著低于AMI组水平(P<0.05)。AMI组大鼠血清中的IL-6、TNF-α、CRP等水平均显著高于假手术组大鼠(均P<0.01);而瑞舒伐他汀组大鼠的IL-6、TNF-α、CRP等水平则显著低于AMI组大鼠(均P<0.05)。AMI组大鼠的ROCK1和ROCK2的表达水平分别为(1.07±0.06)和(1.49±0.04)均显著高于假手术组大鼠,两组比较差异具有统计学意义(均P<0.05);而瑞舒伐他汀组大鼠的ROCK1和ROCK2的表达水平显著低于AMI组大鼠(均P<0.05)。结论对于大鼠急性缺血导致心肌细胞凋亡现象瑞舒伐他汀能够起到较好地缓解效果,其可能的作用机制为对Rho A/ROCK活化和介导的炎症及氧化应激反应进行有效的抑制。
Objective T-investigate the protective effect-f rosuvastatin-n myocardial cells in rats with acute myocardial infarction and the mechanism-f RhoA/ROCK activation.Methods Selected 40 SD rats with similar physiological conditions,and in accordance with the rand-m number table meth-d,the rats were devided into f-ur groups:rosuvastatin group,AMI(acute myocardial infarction model rats group)group and sham group(sham operation group)and control group(normal group),average(n]10);interleukin IL-6(IL-6),the level-f tumor necrosis factor-a(TNF-a),CRP and were detected by ELISA;CK,MDA,SOD and lactate dehydro-genase(The expression level-f LDH)was detected by reagent box meth-d.HE staining was used to detect the pathological changes of rat heart tissue The rat myocardial cell apoptosis situation was detected by transferase mediated nick end labeling(TUNEL);use TTC/Evans blue assay test rats relative myocardial infarction area;using Western blot meth-d for detection of rat in vivo NF-aB p65,R-ck1 and R-ck2,Bcl-2,Bax expression level.Results Rosuvastatin cutting statins group rat infarction area down to(30.00N±7.00N),significantly lower than that in the AMI grou(43.00N±5.00%)(P<0.05);LDH and CK of serum of rosuvastatin group were were significantly lower than those of rats in AMI group(all P<0.05).Cardiac muscle tissue and the level of SOD(serum an-tioxidant molecules)of AMI group decreased sharply compared with the sham group.Meanwhile level of MDA(oxidative damage molecular)-fAMI group was significantly higher than that of sham group(P<0.01),level of MDA of rosuvastatin group was signifi-cantly lower than the level of AMI group(P<0.05).IL-6,TNF-a,CRP of AMI group were significantly higher than sham group(P<0.01);IL-6,TNF-a,CRP of rosuvastatin group were significantly lower than the expression levels of AMI group(P<0.05).Expression levels of R-ck1 and R-ck2 of AMI g-rup,respectively(1.07±0.06)and(1.49±0.04),were significantly higher than those in sham group(0.41±0.04 vs 0.53±0.03).The differences of the two groups were statistically significant(P<0.05).While the expression levels of and ROCK1 and R-ck2 of rosuvastatin group were significantly lower than those of AMI group(all P<0.05).Conclusions Rosuvastatin can play a better mitigated effects on myocardial apoptosis in rats with acute myocardial ischemia and the possible mechanism for effective inhibition on the activation of RhoA/r-ck and mediated inflammation and oxidative stress reaction.
作者
葛水秀
GE Shui-xiu(Anhui Province Xuancheng City Central Hospital,Atihiu 242000,China)
出处
《心脑血管病防治》
2018年第2期98-101,172,共4页
CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT
