Hedgehog通路蛋白在慢性胰腺炎大鼠中的表达

Expression of hedgehog signal pathway in rats with chronic pancreatitis

目的检测慢性胰腺炎（CP）组织中hedgehog信号通路相关蛋白Pteh、Smo和Glil的表达，探讨其意义。方法60只SD大鼠按数字表法随机分为CP组（50只）和对照组（10只）。经尾静脉注射二丁基二氯基锡（DBTC）溶液8mg·ml^-1·kg“方法制备CP模型；对照组尾静脉注射100％乙醇和甘油配制成的有机溶剂1ml／kg体重。6周后处死动物，取胰腺组织常规病理检查，Siriusred染色测定胶原含量，免疫组化和RT—PCR法检测Ptch、Smo、Gli1蛋白及mRNA的表达。结果制模后6周34只大鼠发展为CP，制模成功率为73．9％（34／46）。CP大鼠胶原含量显著高于对照组，差异有统计学意义[（38．52±6．49）％比（7．37±2．28）％，P〈0．05]；Ptch、Smo、Gli 1蛋白阳性表达率分别为73．5％、64．7％和52．9％；Ptch、Smo、Gli1 mRNA表达量分别为2．38±0．42、3．85±1．03、4．63±1．49，均显著高于对照组的蛋白无表达及mRNA的表达（0．23±0．16、0．14±0．05、0．57±0．12，P值均〈0．05）。结论CP组大鼠胰腺组织Pteh、Smo、Gli11均呈高表达，表明hedgehog信号通路参与胰腺慢性炎症反应和纤维化进程。

Objective To explore the expression and significance of hedgehog signal molecules （ Ptch, Smo and Glil ） in chronic pancreatitis tissues in rats. Methods Sixty SD rats were randomly divided into CP group （n =50） and control group （n = 10）. DBTC solvent （8 mg. ml^-1.kg^-1 ） was injected into the rat via tail vein in CP group. In control group, rats were treated only with the solvent at a dose of lml/kg body weight. All rats were sacrificed 6 weeks later to observe the pancreatic pathologic changes. Collagen accumulation in pancreatic sections was determined by staining for Sirius red. Expressions of Ptch, Smo, Glil mRNA and protein in pancreatic tissues were assessed by RT-PCR and immunohistoehemistry. Results The rate of chronic pancreatitis development in rats in CP group within six weeks was 73.9%. Collagen content was markedly higher in CP group than that in control group [ （ 38.52 ± 6.49 ） % vs （ 7.37 ± 2.28 ） %, P 〈 0.05 ]. No Path, Smo, Glil protein expression was observed in normal pancreatic tissues in control group. The positive rate of Pteh, Smo, Gli 1 expression was 73.5%, 64.7% and 52.9% in CP group, and the difference between the two groups was statistically significant （P 〈 0.05 ）. The expressions of Ptch, Smo, Glil mRNA were 2.38 ~ 0.42, 3.85± 1.03, 4.63 ± 1.49 in CP group, which were significantly higher than those in control group （0.23 ±0.16, 0.14 ±0.05, 0.57 ±0.12, P 〈0.05）. Conclusions The Ptch, Smo, Glil was highly expressed in pancreatic tissues in CP rats, suggests hedgehog messenger pathway may play an important role in the chronic inflammation and fibrosis of chronic pancreatitis.