内皮素受体拮抗剂CPU0213和钙拮抗剂CPU86017改善异丙肾上腺素诱导的大鼠心衰的作用机制

Mechanism of endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 ameliorated rats′ heart failure induced by isoproterenol

为了验证内皮素受体拮抗剂CPU0213和钙拮抗剂CPU86017改善异丙肾上腺素(isoproterenol,ISO)诱导的大鼠心衰的分子生物学机制,将SD大鼠均分为5组:正常组、ISO组、药物治疗组(3组)。除正常组外,其余4组均皮下给予异丙肾上腺素(ISO,1 mg/kg,10 d),其中3个治疗组于第10,11天分别皮下注射:氨基胍(30 mg/kg)、CPU0213(30 mg/kg)和CPU86017(4 mg/kg)。结果发现,ISO组,内皮素受体A(ETA)、iNOS、衰老蛋白p66Shc、ε型蛋白激酶C(PKCε)、瘦素受体(OBRb)、NADPH氧化酶p67phox、瘦素(leptin)mRNA或蛋白表达均上调,药物治疗后对这些异常均有逆转。CPU0213和CPU86017均通过抑制内皮素受体和氧化应激及下调p66Shc和PKCε等相关分子表达,减轻ISO引起的心衰。

The purpose of this experiment was to verify whether endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 improved isoproterenol（ISO）-induced heart failure in rats by inhibiting p66Shc and PKCε.40 SD male rats were randomly divided into 5 groups.Except for the normal group,the other groups were given isoproterenol for 10 d（1mg/kg,sc）.Three treatment groups（sc,mg/kg,from day 10-11） included： aminoguanidine group 30 and CPU0213 group 30 and CPU86017 group 4.It was found that mRNA or the protein expressions of endothelin receptor A（ETA）,iNOS,p66Shc,PKCε,OBRb,NADPH oxidase p67phox and leptin increased in ISO group.After drug treatment,the above abnormal indicators were mitigated and even reversed.Hence,it suggested that CPU0213 and CPU86017 improved the ISO-induced heart failure by inhibiting the endothelin receptor and oxidative stress and down-regulating the expressions of p66Shc and PKCε.