加兰他敏对心肌缺血再灌注损伤大鼠血清CK-MB活性及TNF-α和IL-6水平的影响

Effects of Galantamine on Serum CK-MB activity,TNF-α Level and IL-6 Level of Rats with Myocardial Ischemia and Reperfusion Injury

目的:探讨加兰他敏对心肌缺血再灌注损伤(MIRI)大鼠血清肌酸激酶(CK-MB)活性和肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平的影响。方法:SPF级雄性SD大鼠50只,随机均分为假手术组、心肌缺血再灌注(I/R)组、加兰他敏组、联合A组及联合B组;在5组大鼠左冠状动脉前降支(LAD)下穿线,假手术组穿线不结扎,其余4组大鼠穿线后结扎LAD 30 min后,再松开结扎线再灌注120 min,制作I/R模型,假手术组及I/R组造模前30 min静脉注射生理盐水(2 m L/kg),其余3组注射加兰他敏(4 mg/kg),联合A组在造模前45 min还注射阿托品(4 mg/kg)、联合B组在造模前45 min还切断两侧迷走神经;5组大鼠再灌注120 min后,测定大鼠血清CK-MB活性及TNF-α、IL-6水平,取心肌组织进行HE染色,光镜下观察心肌结构。结果:与假手术组比较,I/R组CK-MB活性、TNF-α及IL-6水平升高(P<0.05),提示造模成功;与I/R组比较,加兰他敏组CK-MB活性、TNF-α和IL-6水平降低(P<0.05);与加兰他敏组比较,联合A组及联合B组CK-MB活性、TNF-α和IL-6水平升高(P<0.05);400×光镜视野下见假手术组心肌纤维排列整齐,I/R组心肌结构紊乱,可见细胞坏死和炎性细胞浸润,加兰他敏组心肌纤维排列较整齐,仅见水肿和少许炎性浸润,联合A组及联合B组心肌细胞排列紊乱,心肌水肿,组织间隙有炎性细胞浸润。结论:加兰他敏可能通过胆碱能抗炎通路减少炎性因子的产生,从而减轻心肌MIRI。

Objective： To explore the effect of galantamine on serum CK-MB activity,TNF-α level and IL-6 level of rats with MIRI. ethods： Fifty male SD rats were randomly divided into 5 groups（ n =10） ： group A（ sham operation）,group B（ ischemia / reperfusion,I / R）,group C（ galantamine ＋ I /R）,group D（ atropine ＋ galantamine ＋ I / R）,group E（ bilateral cervical vagotomy ＋ galantamine ＋ I /R）. The rat ischemia / reperfusion injury model was established by ligation of left anterior coronary descending branch（ LAD） for 30 min followed by reperfusion for 120 min. Group A（ sham operation）,group B（ ischemia / reperfusion,I / R） were injected with physiological saline 30 min before model building（ 2 m L / kg） while other groups were injected with galantamine（ 4 mg / kg）. Group D was injected with atropine 45 min before model building（ 4 mg / kg） besides galantamine injection and in group E bilateral cervical vagotomy of rats were cut off besides galantamine injection. 120 min after reperfusion,serum CK-MB activity,TNF-α and IL-6 level were measured. The myocardial tissue was collected to make HE staining,and the myocardial structure was observed under optical microscope.Results： Compared with group A（ sham operation）,the serum CK-MB activity,serum levels of TNF-α and IL-6 were significantly increased in group B（ I /R）,P〈0. 05,suggesting that I /R model was successfully constructed. Compared with group B（ I / R）,the serum CK-MB activity,serum levels of TNF-α and IL-6 in group C（ galantamine ＋ I / R） were significantly decreased（ P〈0. 05）. Compared with group C（ galantamine ＋ I / R）,the serum CK-MB activity,serum levels of TNF-α and IL-6 in group D（ atropine ＋ galantamine ＋ I / R） and group E（ bilateral cervical vagotomy ＋ galantamine ＋ I /R） were increased significantly（ P〈0. 05）. Under 400 × optical microscope,cardiac muscle fibers arranged neatly in group A（ sham operation） while myocardial structure was in disorder,and meronecrobiosis and inflammatory cell infiltration could be seen in group B（ I / R）. In group C（ galantamine ＋I / R）,cardiac muscle fibers arranged neatly,and hydroncus and inflammatory cell infiltration could be seen to some extent while in group D and group E myocardial structure was in disorder,and myocardial edema and inflammatory cell infiltration in interstitial space could be seen. Conclusion： Galantamine may attenuate the myocardial I / R injury by inhibiting the production of inflammatory cytokines through cholinergic anti-inflammatory pathway.