α-生育酚对慢性胰腺炎大鼠胰腺纤维化的影响

The effect of α-tocopherol on fibrosis of chronic pancreatitis rat

目的观察抗氧化剂α-生育酚对慢性胰腺炎（cP）大鼠胰腺纤维化的作用，探讨其机制。方法雄性Wistar大鼠按完全随机法分为对照组、ANP组、α-生育酚组。采用尾静脉单次注射8mg／kg体重二丁基二氯化锡（dibutyltindichloride，DBTC）造模。造模24h后，α-生育酚组大鼠给予800mg／kg体重的α-生育酚灌胃，每日1次，持续4周。ANP组和对照组给予0．6ml色拉油灌胃。4周后处死大鼠，取胰腺组织行病理评分及胶原染色，检测胰腺组织丙二醛（MDA）和羟脯氨酸水平，实时定量PCR法检测胰腺组织TGF—β1mRNA表达。结果灌胃4周后，α-生育酚组大鼠胰腺组织炎症、纤维沉积、异常结构等损伤均较ANP组明显减轻；胰腺组织MDA和羟脯氨酸水平较ANP组显著降低[（0．40±0．20）nmol／100mg蛋白比（1．07±0．41）nmol／100mg蛋白；（402．49±27．62）μg/g蛋白比（664．92±29．04）μg/g蛋白，P值均〈0．05]；胰腺TGF—β1mRNA表达较ANP组显著降低（2．24±0．89比3．35±0．66，P〈0．05）。结论α-生育酚通过降低cP大鼠的体内氧化应激水平，降低TGF—β1mRNA表达，从而减轻胰腺组织的炎症反应和纤维化程度。

Objective To investigate the effect of α-tocopherol on fibrosis of chronic pancreatitis （CP） rat and explore its mechanism. Methods Male Wistar rats were randomly divided into control group, acute neerotizing pancreatitis （ANP） group, α-tocopherol group. CP was induced by dibutyltindich loride （8 mg/kg） infusion into the tail vein. Gastric lavage of α-tocopherol （800 mg/kg body weight, daily） was started 24 hours after dibutyltindich loride infusion for 4 weeks. The rats in ANP and control group received 0.6 ml salad oil gastric lavage. The rats were sacrificed 4 weeks later. Pancreatic tissue was harvested for histological examination and collagen staining, and measurement of the levels of hydroxyproline and malondialdehyde （MDA） of the pancreas were performed. The mRNA expression of transforming growth factor （TGF）-β1 was measured by real time PCR. Results After gastric lavage for 4 weeks, the pancreatic tissue inflammation, fiber deposition and abnormal structure in rats of α-tocopherol group were greatly reduced. The levels of MDA and hydroxyproline in rats of α-tocopherol group were significantly lower than those in ANP group [ （ 0.40±0.20） vs （1.07 ±0.41） nmol/100mg, （402.49 ±27.62） vs （664.92 ±29.04） μg/g, P〈0.05]- The expressions of TGF-β1 mRNA in rats of α-tocopherol group were significantly lower than those in ANP group （2.24 ± 0.89 vs 3.35 ± 0.66, P 〈 0.05 ）. Conclusions Tocopherol gamma can improve pancreatic inflammation and fibrosis by reducing the oxidative stress level and down-regulating the expression of TGF- β1mRNA in rats with CP.