选择性阻断cGMP依赖性蛋白激酶对内毒素孵育的大鼠血管环收缩功能的影响

摘要

目的 观察选择性阻断cGMP依赖性蛋白激酶(PKG)对恢复内毒素(LPS)孵育的大鼠血管环收缩功能的影响.方法 取SD大鼠胸主动脉血管环,随机分为正常对照组(生理盐水)、LPS组(75μg/mL LPS)、N-硝基精氨酸甲酯(L-NAME)组(75μg/mL LPS+0.1 mmol/L L-NAME)和DT-2三氟醋酸盐(DT-2)组(75μg/mL LPS+0.002 mmol/L DT-2).在体外测定LPS孵育2、3、4 h后各组血管环在苯肾上腺素(PE)作用下收缩的浓度效应曲线、最大收缩力(Emax)和产生最大收缩力的半数有效浓度(EC 50).结果 LPS孵育后各时间点血管环的收缩浓度效应曲线与对照组比较明显降低(P＜0.05).L-NAME可以提高LPS孵育2、3、4 h时血管环的收缩功能,Emax和EC50较LPS组差异有统计学意义(P＜0.05).DT2可以显著提高LPS孵育3 h时血管环的收缩功能(P＜0.01),Emax和EC50的差异具有统计学意义(P＜0.01),但在2 h和4 h时,DT-2组与LPS组血管环收缩的浓度效应曲线比较差异无统计学意义(P＞0.05).结论 选择性阻断cGMP依赖性蛋白激酶可以部分恢复LPS孵育的大鼠胸主动脉血管环的收缩功能.%Objective To investigate the effects of selective blockade of cGMP-dependent protein kinase ( PKG) on contractility of vascular rings incubated with lipopolysaccharide ( LPS) in rats. Methods Thoracic aortic rings of SD rats were obtained, and were randomly divided into control group, LPS group, Nω-Nitro-L-arginine methyl ester ( L-NAME) group and DT-2 trifluoroacetate salt group ( DT-2 group). The contraction concentration-response curve, maximal tension ( Emax) and concentration required for half maximal response (EC50) of vascular rings to phenylephrine (PE) were measured in vitro at different time points (2 h, 3 h and 4 h after incubation with LPS) in each group. Results The contraction concentration-response curves of vascular rings after incubation with LPS for different time were significantly lower than those of control group (P <0.05). L-NAME effectively improved the contractility of vascular rings after incubation with LPS for 2 h, 3 h and 4 h, and EC50 and Emax were significantly different from those of LPS group ( P < 0. 05). DT2 significantly enhanced the contractility of vascular rings after incubation with LPS for 3 h ( P < 0. 01), and EC50 and Emax were significantly different from those of LPS group ( P < 0. 01), while there was no significant difference in contraction concentration-response curves between DT-2 group and LPS group at the time points of 2 h and 4 h ( P > 0. 05). Conclusion Selective blockade of PKG can partially recover the contractility of thoracic aortic rings incubated with LPS in rats.