UFP-101对脓毒症大鼠心功能及心脏HMGB1、TLR-4蛋白表达的影响

Effect of UFP-101 on cardiac dysfunction and the myocardial expressions of HMGB1 and TLR4 proteins in septic rats

目的分析脓毒血症大鼠应用内源性孤啡肽受体拮抗剂(UFP-101)对心功能及心肌组织高迁移率族蛋白(HMG)B1,Toll样受体(TLR4)表达的影响。方法选取雄性SD大鼠60只,随机分为对照(C)组盲肠结扎穿孔(CLP),U组(UFP-101),假手术(S)组,采用盲肠结扎穿孔法建立大鼠脓毒血症模型,术后各组经过给药(或生理盐水)处理后分别观察术后12 h,24 h大鼠心功能(每个时间节点10只大鼠);检测血清白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、HMGB1;心肌组织HMGB1及TRL4表达水平及mRNA水平,对比3组测定结果差异。结果与S组比较,C组与U组术后12 h与术后24 h时左心室舒张末期压(LVEDP)、左心室收缩压(LVSP)、平均动脉压(MAP)、等容收缩期左心室内压力上升的速率(+dP/dt)、等容舒张期左心室压力下降的速率(-dP/dt)、心率均明显下降,U组较C组各心功能明显改善(均P<0.05);U组、C组各时间段心肌细胞水肿,炎性细胞浸润明显,各时间段血清IL-6、TNF-α、HMGB1较S组均明显升高,但U组较C组明显下降(均P<0.05);U组与C组各时间段心肌组织HMGB1与TLR4蛋白及mRNA表达,较S组均明显升高,U组较C组表达明显下降(均P<0.05)。结论UFP-101能明显改善脓毒症大鼠心功能并且可能通过影响心肌组织内HMGB1、TLR4的表达引起该作用。

Objective To analyze effects of UFP-101(endogenous endorphin antagonist)on cardiac function and expressions of high migration group protein(HMG)B1 and toll-like receptor(TLR)4 in myocardial tissue in septic rats.Methods 60 male SD rats were selected,and randomly divided into C group(CLP,control group),U group(endogenous solitary brown peptide antagonists UFP-101)and S group(sham group).Scecum ligation perforation method was adopted to establish the rat model of sepsis and rats of each group were treated with drug or saline after operation.After operation 12 h,24 h,cardiac function was observed(10 rats each time point),serum interleukin(IL)-6,tumor necrosis factor(TNF)-α,and HMGB1 were detected.Expressions of HMGB1 and TLR4 protein and mRNA in myocardial tissue were compared.Results LVEDP,LVSP,MAP,+dP/dt,-dP/dt and heart rate in C group and U group decreased significantly 12 h and 24 h after operation compared with S group(P<0.05),and all cardiac functions in U group were significantly improved compared with C group(P<0.05).Myocardial cell edema and inflammatory cell infiltration were evident in both U group and C group at various time periods.Serum IL-6,TNF-α and HMGB1 in C group and U group were significantly increased in each time period compared with S group(P<0.05),but decreased in U group compared with C group(P<0.05).The expressions of HMGB1,TLR4 proteins and mRNA in myocardial tissues at different time periods were significantly increased in U group and C group compared with group S(P<0.05),and decreased in U group compared with C group(P<0.05).Conclusions UFP-101 could significantly improve the cardiac function of sepsis rats and might cause this effect by affecting the expressions of HMGB1 and TLR4 in myocardial tissue.