乌司他丁和甲基泼尼松龙在婴幼儿体外循环心脏手术中的脑保护作用

Protective effects of ulinastatin and methylprednisolone on brain in infants receiving cardiopulmonary bypass surgery

目的探讨乌司他丁和甲基泼尼松龙在婴幼儿体外循环心脏手术中脑损伤的保护作用。方法 90例先天性心脏病行体外循环心脏手术的婴幼儿分为乌司他丁组30例、甲基泼尼松龙组30例和手术对照组30例,其中乌司他丁组患儿给予10 000u/kg乌司他丁静脉注射,复温后和停机后分别再次给予5 000u/kg乌司他丁;甲基泼尼松龙组患儿在预充液中加入甲基泼尼松龙30mg/kg;手术对照组患儿加入等量生理盐水;选择30例健康婴幼儿作为健康对照组。采用ELISA法检测健康对照组及其他3组患儿手术前(T_0)、体外循环开始30min(T_1)、停体外循环即刻(T_2)、停体外循环6h(T_3)、停体外循环12h(T_4)、停体外循环24h(T_5)、停体外循环48h(T_6)时血清星形胶质细胞S-100β蛋白(astroglial cell S-100βprotein,S-100β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和IL-8水平。结果手术对照组T1~T4时血清S-100β水平[(0.71±0.22)、(0.91±0.27)、(0.77±0.21)、(0.72±0.18)μg/L]高于乌司他丁组[(0.48±0.04)、(0.59±0.14)、(0.51±0.05)、(0.45±0.03)μg/L]、甲基泼尼松龙组[(0.50±0.10)、(0.61±0.16)、(0.50±0.12)、(0.43±0.11)μg/L]和健康对照组[(0.41±0.05)μg/L](P<0.05);手术对照组T1~T5时血清TNF-α水平[(177.4±22.8)、(189.7±26.5)、(182.5±24.3)、(173.2±25.5)、(163.5±18.4)ng/L]和IL-6水平[(67.43±7.46)、(70.04±8.12)、(71.12±7.77)、(67.45±8.11)、(63.24±7.75)ng/L]均高于乌司他丁组[TNF-α(147.4±18.3)、(153.5±23.6)、(146.9±14.7)、(142.8±17.3)、(136.9±15.3)ng/L,IL-6(51.76±7.45)、(58.02±7.43)、(55.34±7.86)、(51.23±7.85)、(51.54±8.04)ng/L]、甲基泼尼松龙组[TNF-α(146.5±19.7)、(152.2±26.4)、(147.8±16.6)、(143.6±18.5)、(137.6±14.8)ng/L,IL-6(51.21±8.03)、(57.78±7.69)、(56.23±8.00)、(53.42±7.76)、(51.12±7.94)ng/L]和健康对照组[TNF-α(135.1±20.4)ng/L、IL-6(43.23±7.87)ng/L](P<0.05);手术对照组T1~T5时IL-8水平[(1.11±0.10)、(1.13±0.09)、(1.12±0.11)、(0.92±0.05)、(0.74±0.04)μg/L]高于乌司他丁组[(0.67±0.09)、(0.70±0.07)、(0.72±0.09)、(0.65±0.06)、(0.51±0.07)μg/L]、甲基泼尼松龙组[(0.69±0.08)、(0.72±0.08)、(0.74±0.10)、(0.64±0.07)、(0.53±0.08)μg/L]和健康对照组[(0.41±0.04)μg/L](P<0.05);不同时间点乌司他丁组与甲基泼尼松龙组血清S-100β、TNF-α、IL-6和IL-8水平比较差异均无统计学意义(P>0.05)。结论乌司他丁和甲基泼尼松龙在婴幼儿体外循环心脏手术中具有脑保护和抑制炎症反应的作用。

Objective To explore the protective effect of ulinastatin and methylprednisolone on brain in infants receiving cardiopulmonary bypass(CPB)surgery.Methods Ninety infants with congenital heart disease undergoing CPB were divided into ulinastatin group,methylprednisolone group and operation control group,with 30 patients in each group.Ulinastatin group was intravenously injected with 10 000u/kg ulinastatin,followed by 5 000u/kg ulinastatin after re-warming and CPB ending.Methylprednisolone group was added 30 mg/kg methylprednisolone into the pre-filled solution.Operation control group was replaced with equivalent volume of normal saline.Another 30 healthy infants were as controls(healthy control group).The levels of serum astroglial cell S-100βprotein(S-100β),tumor necrosis factor-α(TNF-α),interleukin(IL)-6and IL-8were detected by ELISA before operation(T_0),in 30 min after CPB(T_1),at the ending of CPB(T_2),in 6hafter CPB ending(T_3),in 12 hafter CPB ending(T_4),in 24 hafter CPB ending(T_5),and in 48 hafter CPB ending(T_6)in all groups.Results The S-100βlevels at the time points of T1-T4 were significantly higher in operation control group((0.71±0.22),(0.91±0.27),(0.77±0.21),(0.72±0.18)μg/L)than those in ulinastatin group((0.48±0.04),(0.59±0.14),(0.51±0.05),(0.45±0.03)μg/L),methylprednisolone group((0.50±0.10),(0.61±0.16),(0.50±0.12),(0.43±0.11)μg/L),and healthy control group((0.41±0.05)μg/L)(P<0.05).The levels of TNF-α((177.4±22.8),(189.7±26.5),(182.5±24.3),(173.2±25.5),(163.5±18.4)ng/L)and IL-6((67.43±7.46),(70.04±8.12),(71.12±7.77),(67.45±8.11),(63.24±7.75)ng/L)in operation control group at the time points of T1-T5 were significantly higher than those in ulinastatin group((147.4±18.3),(153.5±23.6),(146.9±14.7),(142.8±17.3),(136.9±15.3)ng/L;(51.76±7.45),(58.02±7.43),(55.34±7.86),(51.23±7.85),(51.54±8.04)ng/L),methylprednisolone group(146.5±19.7),(152.2±26.4),(147.8±16.6),(143.6±18.5),(137.6±14.8)ng/L;(51.21±8.03),(57.78±7.69),(56.23±8.00),(53.42±7.76),(51.12±7.94)ng/L)and healthy control group((135.1±20.4),(43.23±7.87)ng/L)(P<0.05).The IL-8levels at the time points of T1-T5 were significantly higher in operation control group((1.11±0.10),(1.13±0.09),(1.12±0.11),(0.92±0.05),(0.74±0.04)ng/mL)than those in ulinastatin group((0.67±0.09),(0.70±0.07),(0.72±0.09),(0.65±0.06),(0.51±0.07)μg/L),methylprednisolone group((0.69±0.08),(0.72±0.08),(0.74±0.10),(0.64±0.07),(0.53±0.08)μg/L),and healthy control group((0.41±0.04)μg/L)(P<0.05).There were no significant differences in the levels of S-100β,TNF-α,IL-6and IL-8between ulinastatin group and methylprednisolone group(P>0.05).Conclusion Ulinastatin and methylprednisolone can protect the brain and suppress inflammation in infants receiving CPB surgery.