色甘酸钠抑制肠组织蛋白酶活化受体-2表达对大鼠肠缺血再灌注损伤的影响

Effects of cromolyn sodium on intestinal ischemia-reperfusion injury by inhibiting PAR-2 expressionin rats

目的探讨再灌注前应用色甘酸钠对大鼠肠缺血再灌注损伤的影响及与肥大细胞（MC）激活、肠组织蛋白酶活化受体-2（PAR-2）受体表达的关系。方法32只SD大鼠通过数字随机法分为4组：假手术组（S组）、缺血再灌注组（ⅡR组）、色甘酸钠组（CS组）、Compound 48／80组（CP组）。每组8只。复制大鼠肠缺血再灌注损伤模型，CS、CP组在再灌注前5min分别经尾静脉给予色甘酸钠25、0．75mg,／kg，s、ⅡR组分别给予等量的生理盐水。再灌注3h后活杀大鼠取小肠组织。观察各组肠黏膜病理变化；免疫组化观察类胰蛋白酶表达及MC数量；免疫印迹（Western blot）检测肠组织PAR-2表达。结果s组肠黏膜Chiu’s病理评分（0．75±0．21）、MC数量（10±3）、类胰蛋白酶表达（125±15）和肠组织PAR-2受体表达（109±10）最少（P〈0．05），CP组病理评分（5．12±0．83）、MC数量（36±6）、类胰蛋白酶表达（192±18）和肠组织PAR-2受体表达（211±14）均最多（P〈0．05）；CS组肠黏膜Chiu’s病理评分（2．14±0．64）、MC数量（15±4）、类胰蛋白酶表达（138±17）和肠组织PAR-2受体表达（124±12）均明显少于IIR组和CP组（P〈0．05）。结论色甘酸钠可能通过稳定肥大细胞膜，抑制类胰蛋白酶表达，进而抑制PAR-2信号通路，从而减轻肠缺血再灌注所致肠损伤。

Objective To explore the effects of cromolyn sodium （CS） on intestinal ischemia- reperfusion （ⅡR） and its relationship with mast cell activation and protease-activated receptor 2 （PAR-2） expression. Methods A total of 32 SD rats were randomly divided into 4 groups： sham-operated （ S ） , intestinal ischemia reperfusion （ⅡR）, CS （a mast cell stabilizer, CS, 25 mg/kg） and compound 48/80 （a mast cell degranulator, CP, 0. 75 mg/kg） （n = 8 each）. ⅡR was induced by clamping superior mesenteric artery for 75 rain followed by reperfusion for 3 hours. The above agents were intravenously administrated at 5 rain pre-reperfusion. Rats were then sacrificed and intestinal issues harvested for histological examinations. The tryptase expression and mast cell count were analyzed by immunohistochemistry. PAR-2 was analyzed by Western blot. Results The Chiu＇s score （0. 75 ± 0. 21 ）, mast cell count （ 10 ± 3 ） , tryptase expression （125 ± 15） and PAR-2 expression （109 ± 10） of group S were the least while those of group CP the most （ all P 〈 0. 05 ）. The Chiu＇s score （2. 14 ± 0. 64 ）, mast cell count （ 15 ± 4 ）, tryptase expression （ 138 ± 17） and PAR-2 expression （124 ± 12） of group CS were less than those of groups IIR and CP （all P 〈 0. 05）. Conclusion Cromolyn sodium may reduce IIR injury by stabilizing mast cell membrane and inhibiting the expressions of tryptase and PAR-2.