Caspase-1抑制剂在野百合碱诱导的肺动脉高压大鼠中的作用

发布时间：2019-04-28 19:37

【摘要】：目的研究天冬氨酸特异性半胱氨酸蛋白酶-1(caspase-1)及其抑制剂在肺动脉高压(PAH)大鼠中的作用,探究PAH的发病机制。方法 SD大鼠36只,随机分为3组:对照组、肺动脉高压组(MCT组)、ACYVAD-CMK组(YVAD组)。YVAD组腹腔注射caspase-1抑制剂AC-YVAD-CMK药物0.5 h后腹腔注射野百合碱(60 mg/kg),而MCT组腹腔注射同剂量生理盐水0.5 h后腹腔注射等剂量的野百合碱,对照组则给予等剂量的生理盐水处理。正常饲养21 d后留取组织标本,测量肺动脉压力[右心室收缩压(RVSP)],计算右室肥厚指数{右心室/(左心室+心室隔)[RV/(LV+S)]比值},行HE染色观测各组形态学变化,免疫组化检测各组caspase-1、白细胞介素-1β(IL-1β)的表达水平。结果 (1)与对照组相比,MCT组及YVAD组RVSP、RV/(LV+S)值均明显增高(P0.05);与MCT组相比,YVAD组的RVSP、PV/(LV+S)值又明显下降(P0.05)。(2)病理组织学检查结果显示,AC-YVAD-CMK可减轻PAH模型大鼠肺小动脉内膜增生,减少肺组织炎性细胞浸润。(3)免疫组化结果显示,AC-YVAD-CMK可减少caspase-1、IL-1β的表达。结论 AC-YVAD-CMK可抑制caspase-1的活化,减少IL-1β的分泌,进而减轻PAH的发生、发展。
[Abstract]:Aim to investigate the role of aspartate specific cysteine protease-1 (caspase-1) and its inhibitor in (PAH) rats with pulmonary hypertension and to explore the pathogenesis of PAH. Methods 36 SD rats were randomly divided into three groups: control group, pulmonary hypertension group (MCT group). ACYVAD-CMK group (YVAD group). YVAD group) received intraperitoneal injection of caspase-1 inhibitor AC-YVAD-CMK for 0.5h and then intraperitoneal injection of monocrotaline (60 mg/kg). The same dose of monocrotaline was injected intraperitoneally in the MCT group and the control group was treated with the same dose of saline after intraperitoneal injection of the same dose of saline for 0.5h. After 21 days of normal feeding, the pulmonary artery pressure [right ventricular systolic pressure (RVSP)] was measured and the right ventricular hypertrophy index {right ventricular / (left ventricular septum) [RV/ (LV S)] ratio} was calculated. The morphological changes of each group were observed by HE staining, and the expression level of caspase-1, interleukin-1 尾 (IL-1 尾) was detected by immunohistochemistry. Results (1) compared with the control group, the RVSP,RV/ (LV S) values in MCT group and YVAD group were significantly higher than those in control group (P0.05). Compared with the MCT group, the RVSP,PV/ (LV S) value of the YVAD group was significantly lower (P0.05). (2). The results of histopathological examination showed that AC-YVAD-CMK could reduce the intimal proliferation of the pulmonary arterioles in the PAH model rats. (3) Immunohistochemistry showed that AC-YVAD-CMK could decrease the expression of caspase-1,IL-1 尾. Conclusion AC-YVAD-CMK can inhibit the activation of caspase-1, decrease the secretion of IL-1 尾, and then reduce the occurrence and development of PAH.
【作者单位】：广州中医药大学;广州军区广州总医院心血管外科中心;广东省人民医院心血管病研究所;广州市红十字会医院心血管外科;
【基金】：广东省自然科学基金资助项目(编号:2015A03031362)
【分类号】：R544.1

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