轻症急性胰腺炎时细胞免疫功能变化的实验研究

Experimental Research on Cellular Immunological Alteration in Mild Acute Pancreatitis

背景:胸腺素α1(TA1)是一种具有免疫调节活性的多肽激素,临床应用已日益广泛,具有抗衰老、抗肿瘤、抗感染、促进伤口愈合等作用,但TA1是否对轻症急性胰腺炎(MAP)具有治疗作用尚不十分清楚。目的:研究MAP时细胞免疫功能的变化,并通过给予外源性TA1观察能否减轻MAP的严重程度。方法:54只雄性Sprague-Dawley大鼠随机分为对照组、MAP组和TA1治疗组。MAP模型采用雨蛙肽(20μg／kg)腹腔注射,1次／h,共4次,建立大鼠MAP模型;TA1组于造模成功后立即皮下注射TA1(100μg／kg);对照组仅给予腹腔注射生理盐水。三组大鼠分别在造模后 3 h、6 h、12 h处死,收集外周血和胰腺标本。观察MAP时TA1对血清淀粉酶、血清肿瘤坏死因子(TNF)-α和胰腺组织炎症评分的影响;同时应用流式细胞仪观察外周血CD3+、CD4+、CD8+T细胞的变化。结果:MAP组与TA1组各时间点的血清淀粉酶、血清TNF-α水平和胰腺组织炎症评分均显著高于对照组(P<0．01),但MAP组与TA1组之间无显著差异(P>0．05)。MAP组6 h CD8+T细胞百分率明显低于对照组(P<0．05),CD4+／CD8+比值明显高于对照组(P< 0．05):MAP组其他时间点和TA1组与对照组比较无显著差异(P>0．05)。结论:MAP早期存在细胞免疫功能失调,但可通过自身调节维持正常的免疫功能。MAP时应用TA1对细胞免疫功能可能具有调节作用。

Thymosin alpha 1 （TA1） is a hormone produced by thymic stromal cells having immunoloregulating function. It has been widely used in clinic, and has been shown to have antl-aging, anti-tumor, anti-infective and wound healing properties. The potential therapeutic efficacy of TA1 in mild acute pancreatitis （MAP） is not yet clear. Aims： The aim of this study was to investigate the cellular immunological alteration and to observe the efficacy of exogenous TA1 in MAP of rats. Methods： Fifty-tour male Sprague-Dawley rats were randomly allocated into 3 groups： control group, MAP group and TA1-treated group. MAP model was constructed by intraperitoneal injection of eerulein （20 μg/kg）, repeated every 1 hour for 4 times, while the control group was given intraperitoneal injection of physiological saline only. In the treated group, TA1 was administrated once at the dose of 100 μg/kg by subcutaneous injection after the initiation of MAP. All the rats were sacrificed at 3 hours, 6 hours and 12 hours, respectively, after the construction of the model. Blood samples and pancreatic tissue specimens were harvested. The serum levcls of amylase and tumor necrosis tactor （TNF）-α were detected and the histological scores of pancreatic tissue change were assessed independently by two pathologists. Besides, the percentage of CD3＋/CD4＋/CD8＋T cells in the peripheral blood mononuclear cells were determined hy flow cytometry （FCM）. Results： The levels of serum amylase, serum TNF-α and histological score increased significantly in MAP and TA1-treated group （P〈0.01, respectively） at 3 hours, 6 hours arid 12 hours, There was no significant difference between MAP and TA1-treated group. In MAP group, the percentage of CD8＋T cells decreased significantly （P〈0.05）, and the ratio of CD4＋/CD8＋ increased markedly at 6 hours as compared with the controls. No significant difference was found at other time points. The percentages of CD3＋/CD4＋/CD8＋T cells in TA1-treated groups were not significantly different from that of the controls at all the time points tested. Conclusions： The present study indicates that cellular immunological imbalance occurs in case of MAP, meanwhile, it can be normalized by self-regulation. It also seems that TA1 may have some effects on cellular immunity in MAP.