Maulik N, Engelman R M, Wei Z, Lu D, Rousou J A, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110.
Circulation. 1993 Nov;88(5 Pt 2):II387-94.
Interleukin-1 (IL-1) has been shown to induce superoxide dismutase (SOD) activity and to express heat shock protein (HSP). Since the reperfusion of ischemic heart is associated with the reduction of antioxidative enzymes including SOD and expression of HSP, it was hypothesized that IL-1 could be beneficial against ischemic reperfusion injury.
Rats were injected with recombinant IL-1 alpha (30 micrograms/kg IP); after 48 hours, they were anesthetized and hearts were removed, isolated, and perfused by the Langendorff technique. Myocardial functions were studied by measuring left ventricular developed pressure (LVDP) and its maximum first derivative (LV dP/dt), and cellular injury was studied by estimating creatine kinase (CK) release. Induction of the expression of HSP27 mRNA and HSP27 protein was examined by Western blot analysis and Northern blot analysis, respectively. Antioxidant enzymes were assayed by enzymatic analysis. Our results indicated reduction of ischemic reperfusion injury by IL-1 alpha, as evidenced by better recovery in postischemic ventricular functions (LVDP [mm Hg]: control, 63 +/- 14; IL-1, 102 +/- 11; P < .05), increased coronary flow (mL/min) (control, 2.93 +/- 0.58; IL-1, 5.17 +/- 0.43; P < .03), and reduced creatine kinase release (IU/L) (control, 110 +/- 5.78; IL-1, 81.76 +/- 7.71; P < .01). IL-1 alpha induced the expression of HSP27 mRNA within 2 hours as examined by Northern blot analysis and the expression of HSP27 after 48 hours. In addition, hearts pretreated with IL-1 alpha for 48 hours and then subjected to 30-minute ischemia and 60-minute reperfusion enhanced the activities (nmol/min/mg protein) of Cu/Zn SOD (control, 1.55 +/- 0.22; IL-1 alpha, 2.92 +/- 0.04; P < .004), Mn-SOD (control, 4.54 +/- 0.19; IL-1 alpha, 6.33 +/- 0.09, P < .001), catalase (control, 15.53 +/- 0.37; IL-1 alpha, 21.67 +/- 0.72; P < .002), glutathione peroxidase (control, 17.49 +/- 0.35; IL-1 alpha, 25.87 +/- 0.58; P < .001), and glucose-6-phosphate dehydrogenase (control, 22.71 +/- 0.44; IL-1 alpha, 29.53 +/- 0.48; P < .001).
The results of this study indicate that low doses of IL-1 alpha can be used as a therapeutic agent to precondition a heart from ischemia reperfusion injury.
白细胞介素-1（IL-1）已被证明可诱导超氧化物歧化酶（SOD）活性并表达热休克蛋白（HSP）。由于缺血心脏的再灌注与包括SOD在内的抗氧化酶的减少以及HSP的表达有关，因此推测IL-1可能对缺血再灌注损伤有益。
给大鼠腹腔注射重组IL-1α（30微克/千克）；48小时后，将其麻醉，取出心脏，分离并采用Langendorff技术进行灌注。通过测量左心室舒张末压（LVDP）及其最大一阶导数（LV dP/dt）来研究心肌功能，通过评估肌酸激酶（CK）释放来研究细胞损伤。分别通过蛋白质印迹分析和Northern印迹分析检测HSP27 mRNA和HSP27蛋白表达的诱导情况。通过酶促分析测定抗氧化酶。我们的结果表明IL-1α可减轻缺血再灌注损伤，缺血后心室功能的更好恢复证明了这一点（LVDP[毫米汞柱]：对照组，63±14；IL-1组，102±11；P<.05），冠状动脉血流量增加（毫升/分钟）（对照组，2.93±0.58；IL-1组，5.17±0.43；P<.03），肌酸激酶释放减少（国际单位/升）（对照组，110±5.78；IL-1组，81.76±7.71；P<.01）。通过Northern印迹分析检测，IL-1α在2小时内诱导HSP27 mRNA表达，48小时后诱导HSP27表达。此外，用IL-1α预处理48小时然后经历30分钟缺血和60分钟再灌注的心脏增强了铜/锌超氧化物歧化酶（nmol/分钟/毫克蛋白）的活性（对照组，1.55±0.22；IL-1α组，2.92±0.04；P<.004）、锰超氧化物歧化酶（对照组，4.54±0.19；IL-1α组，6.33±0.09，P<.001）、过氧化氢酶（对照组，15.53±0.37；IL-1α组，21.67±0.72；P<.002）、谷胱甘肽过氧化物酶（对照组，17.49±0.35；IL-1α组，25.87±0.58；P<.001）和葡萄糖-6-磷酸脱氢酶（对照组，22.71±0.44；IL-1α组，29.53±0.48；P<.001）。
本研究结果表明，低剂量的IL-1α可作为一种治疗剂用于使心脏预处理以预防缺血再灌注损伤。
