丹参酮ⅡA 对压力超负荷大鼠心肌血红素加氧酶-1 mRNA 基因表达的作用

摘要

目的：观察丹参酮ⅡA（TanⅡA）对压力超负荷大鼠心肌血红素加氧酶-1（HO -1）mRNA基因表达的影响，并探讨其对心肌纤维化、心室重构的保护作用。方法40只 SD 大鼠随机抽取8只为假手术组，其余32只大鼠为手术组采用腹主动脉缩窄术制备压力超负荷模型，术后手术组存活的22只大鼠再随机分成3组，分别为模型组（n =7）、TanⅡA 组（n =7）及 TanⅡA + HO -1抑制剂处理组[TanⅡA +锌原卟啉（ZnPP）注射液组，n =8）。造模术后第4周开始给药，假手术组、模型组均以0.9%氯化钠注射液4 mL/（kg· d）腹腔注射；TanIIA 组以丹参酮ⅡA 磺酸钠（STS）注射液20 mg/（kg·d）腹腔注射；TanIIA + ZnPP 组以 STS注射液20 mg/（kg·d）+ ZnPP 注射液1 mg/（kg·d）腹腔注射。各组每日上午给药1次，疗程为4周。检测4组大鼠心肌组织 HO -1mRNA 基因表达，观察大鼠心肌组织结构变化。结果 TanⅡA 组 HO -1 mRNA 基因表达高于其余3组（均 P <0.01），当使用 HO -1抑制剂 ZnPP 注射液后可见 HO -1 mRNA 基因表达较 TanIIA明显下降（P <0.01）。光镜下假手术组大鼠心肌纤维排列整齐、横纹明显，胞核结构清晰，无坏死灶，心肌间质及微血管正常；与假手术组比较，模型组心肌纤维明显增粗且排列紊乱，部分胞核固缩，并有局灶性、片状坏死灶和炎性细胞浸润，血管周围及间质有胶原纤维的沉积；TanIIA 组和 TanIIA + ZnPP 组心肌的组织形态学均有不同程度改善，而 TanIIA 组改善更明显。结论 TanⅡA 可以抑制心肌纤维化，减缓心室重构，此作用可能与 TanIIA 诱导 HO -1过表达有关。%Objective To observe the Tanshinone - IIA(TanIIA)on the expression of myocardium hemo oxygenase - 1(HO - 1)mRNA in pressure - overloaded rats,and to investigate its protection of myocardial fibrosis and ventricular remodeling. Methods 40 SD rats were randomly selected 8 for control(sham group),the remai-ning 32 rats were prepared for abdominal aortic constriction pressure - overloaded model. Postoperative survival 22 rats were randomly divided into model group(n = 7),TanIIA group(n = 7)and TanIIA + HO - 1 inhibitor group (TanIIA + ZnPP group,n = 8). Four weeks after the operation,the model was successfully made and began to give medicine for four weeks. The sham group and the model group received intraperitoneal injection of 0. 9% sodium chlo-ride injection(4mL·kg·d). The TanⅡA group received intraperitoneal injection of TanⅡA sulfonate sodium injec-tion(20mg·kg·d). The TanⅡA + ZnPP group received TanⅡA sulfonate sodium injection(20mg·kg·d) combined with ZnPP injection(1mg·kg·d). The expression of HO - 1 mRNA in myocardium was detected,and the pathological HE staining was done at the same time. Results The expression of HO - 1 mRNA in TanIIA group was higher than the other three groups(P < 0. 01). The expression of HO - 1 mRNA in TanIIA + ZnPP group was obviously decreased as compared with TanIIA group(P < 0. 01). Myocardial fibrosis in sham operation group ar-ranged irregularly,visible cross striations,clear nuclei,without necrosed tissue,and with normal myocardial intersti-tium and micrangium. As compared with the sham operation group,the myocardial fibrosis in model group became denser and malalignment,some nucleolus shrinked,with focal and patchy necrosis,inflammatory cell infiltration,deposition of collagen fibers around vessel and mesenchyme. There were different improvements of myocardial tissue morphology in TanIIA and TanIIA + ZnPP group,and the improvement in TanIIA group was more obvious. Conclusion TanIIA can inhibit myocardial fibrosis and reduce ventricular remodeling,which may be related with the TanIIA - induced o-ver - expression of HO - 1.