肾上腺髓质素对大鼠肾脏损伤早期白细胞介素-4及γ-干扰素表达的影响

目的 观察外源性肾上腺髓质素(ADM)对肾脏机械性损伤后γ-干扰素(IFN-γ)、IL-4表达的影响.方法 健康成年普通级Wistar大鼠104只,采用随机数字表法分为四组:正常对照组(8只)、单纯创伤组(32只)、预防组(32只)、治疗组(32只);后三组采用自由落体打击仪直接打击大鼠左侧脊肋区制作肾脏机械性损伤模型.两给药组分别于致伤前、后10 min腹腔注射ADM(0.1 nmol/kg).三组肾脏损伤分别于伤后1,6,12,24 h采用快速心脏采血法处死.提取肾脏,甲醛固定,免疫组织化学染色,观察IFN-γ、IL-4在组织中的表达.结果 (1)IL-4表达:预防组在伤后1 h出现阳性表达,6,12 h阳性表达强度渐升,24 h达高峰,与同时相点单纯创伤组比较,差异有统计学意义(P<0.05);治疗组在伤后1 h升高,6 h达高峰,与同时相点单纯创伤组比较,差异有统计学意义(P<0.05);伤后12 h下降,24 h接近单纯创伤组水平.(2)IFN-γ表达:与同时相点单纯创伤组比较,预防组在伤后6,24 h表达明显升高(P<0.05),12 h表达降低(P<0.05);治疗组在1,12,24 h的表达明显低于单纯创伤组(P<0.05).与正常对照组比较,治疗组在伤后1,12 h明显降低.治疗组各时相点IL-4及INF-γ的表达均较预防组明显下降(P<0.05).单纯创伤组IL-4与IFN-γ水平呈负相关关系,预防组IL-4与IFN-γ间呈正相关关系.结论 IL-4与IFN-γ在肾损伤与修复中发挥拮抗作用.外源性ADM的预防性给药及治疗性给药均对IL-4的表达有增强作用.预防性应用外源性ADM的主要作用在于动态调控IFN-γ的表达.

Abstract：

Objective To observe the effects of exogenous adrenomedullin(ADM)on expressions of IL-4 and IFN-γ following mechanical renal trauma in the rats. Methods A total of 104 healthy adult plain grade Wistar rats were,randomly divided into four groups,ie,normal control group(eight rats),simple trauma group(32 rats),prevention group(32 rats,injected with ADM before trauma)and treatment group(32 rats,injected with ADM after trauma).The experimental model of rat with mechanical renal trauma was prepared by striking the ridge of the left rib area with free dropping forrous hammer in all groups except for the control group.Ten minutes before and after mechanical renal trauma,ADM ly.All rats were sacrificed by draining out all the blood in their hearts at 1,6,12 and 24 hours after mechanical renal trauma.Then,the renal tissues were removed and fixed with 10% formalin for observing the positive expressions of IL-4 and IFN-γ by means of SABC staining. Results Compared with the simple trauma group,the positive expression of IL-4 in the prevention group Wag observed at 1 hour,gradually increased at 6 and 12 hours and reached the peak at 24 hours after mechanical renal trauma,with statistical difference(P<0.05).The positive expression of IL-4 in the treatment group WaS increased at one hour and reached the peak at 6 hours after mechanical renal trauma,with statistical difference(P<0.05).Compared with the simple trauma group,the IFN-γ expression in the prevention group was,increased at 6 and 24 hours but decreased at 12 hour,while that in the treatment group was decreased significantly at 1,12 and 24 hours.Compared with the normal control group,the IFN-γ expression in the treatment group was significantly decreased at 1 and 12 hours.The IFN-γ expression in the treatment group was lower than that in the prevention group at every time points,with statistical difference(P<0.05). Conclusions Preventive and therapeutic administration of exogenous ADM can enhance the expression of IL-4.IL-4 and IFN-γ play an antagonistic role in repair ofthe renal injury.The primary role of exogenous ADM is the dynamic regulation of IFN-γ expression.