Sumitra Miriyala, Manikandan Panchatcharam, Nayeem Mohammed, Manohar Bhakthavatsalam Murali, Lokanadam Beema, Vairamuthu Subbiah, Subramaniam Samu, Puvanakrishnan Rengarajulu
Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
Mol Cell Biochem. 2005 Jan;268(1-2):149-58. doi: 10.1007/s11010-005-3856-8.
This study attempted to probe the role of complement activation in promoting acute myocardial infarction (AMI) induced by coronary artery ligation (CAL) in rats. The surgical technique used in this study significantly reduced early mortality (95% survival rate) and also reduced the variation in infarct size (33+/-1.87%) at 32 h after surgery. Time course studies on the initiation of AMI at various time points were carried out using physiological, biochemical, histopathological and electron microscopical techniques. Serum markers and activities of lysosomal hydrolases were found to be significantly elevated at the 8th hour post ligation. Histological studies showed polymorphonuclear cells emigration and total coagulation necrosis. Transmission electron micrograph exhibited mild distortion of muscle fibres and mitochondrial rupture with disrupted cristae. Immunoblotting studies confirmed the presence of alpha2-macroglobulin which supported the inflammatory response at 8th h of post ligation. The initiation of the complement (C) activation was observed by the increase in the level of the soluble form of the membrane attack complex (sC5b-9) in serum and left ventricle. Immunoexpression studies confirmed the initiation of the terminal C activation as shown by the expression of C5, C6, C7, C8, C9 and sC5b-9 complex at the 8th h of AMI. This study conclusively demonstrated that initiation of the C activation was observed to be significant at the 8th h of AMI induced by CAL in rats.
本研究试图探究补体激活在促进大鼠冠状动脉结扎（CAL）诱导的急性心肌梗死（AMI）中的作用。本研究中使用的手术技术显著降低了早期死亡率（存活率95%），并且在术后32小时也减少了梗死面积的变化（33±1.87%）。使用生理学、生物化学、组织病理学和电子显微镜技术对AMI在各个时间点的起始进行了时间进程研究。发现血清标志物和溶酶体水解酶的活性在结扎后第8小时显著升高。组织学研究显示多形核细胞迁移和完全凝固性坏死。透射电子显微镜照片显示肌纤维轻度扭曲和线粒体破裂，嵴断裂。免疫印迹研究证实了α2-巨球蛋白的存在，这支持了结扎后第8小时的炎症反应。通过血清和左心室中膜攻击复合物可溶性形式（sC5b-9）水平的升高观察到补体（C）激活的起始。免疫表达研究证实了终末C激活的起始，如在AMI第8小时C5、C6、C7、C8、C9和sC5b-9复合物的表达所示。本研究最终证明，在大鼠CAL诱导的AMI第8小时观察到C激活的起始具有显著性。
