Rock2和TGF-β1在哮喘大鼠中的表达及药物干预

Expression of Rock2 and TGF-β1 mRNA and glucocorticoid intervention in asthmatic rats

摘要:

目的：探讨Rho激酶2（Rock2）和转化生长因子-β1（TGF-β1）在哮喘急性发作期的作用及糖皮质激素干预对其表达的影响。方法：48只大鼠随机分为哮喘组（AST组）、对照组（CON组）、地塞米松治疗组（DXM组）和布地奈德治疗组（BUD）4组，每组12只。用改良卵白蛋白进行致敏和激发制备大鼠哮喘模型，观察大鼠肺组织病理变化、分析支气管肺泡灌洗液（BALF）中的细胞计数。采用免疫组织化学法测定Rock2蛋白质表达和原位杂交法测定TGF-β1 mRNA表达。结果：BUD组和DXM组大鼠病理变化较哮喘组明显减轻。哮喘组BALF细胞总数、嗜酸性粒细胞（EOS）、多形核粒细胞（PMN）和淋巴细胞（Lym）百分率均显著高于CON组（P﹤0.01），巨噬细胞（Mф）百分率显著低于对照组（P﹤0.01），而BUD和DXM组中BALF中细胞总数及EOS、Lym百分率低于哮喘组，Mф百分率显著高于哮喘组。哮喘组肺组织中Rock2及TGF-β1 mRNA表达显著高于CON、BUD和DXM组（P﹤0.01），而BUD、DXM组与对照组相比，差异均无统计学意义（P>0.05）。结论：哮喘急性发作期Rock2和TGF-β1的表达显著增加；糖皮质激素干预可降低Rock2和TGF-β1的表达水平，从而减轻哮喘气道炎症。［中国当代儿科杂志，2010，12(11)：877-881］

Abstract:

OBJECTIVE: To study the roles of rhoassociated coiled coil forming protein kinase 2 (Rock2) and transforming growth factor-β1 (TGF-β1) mRNA in acute asthma and the effect of glucocorticoid intervention on the Rock2 and TGF-β1 mRNA expression in rats. METHODS: Forty-eight male rats were randomly divided into 4 groups (n=12 each): asthma, control, dexamethasone treated (DXM) and budesonide treated (BUD). Rat model of asthma was prepared by the ovalbumin (OVA) challenge. The animals were sacrificed 24 hrs after the last challenge. The total cell number and differentiation cell number were counted in bronchoalveolar lavage fluid (BALF). The protein expression of Rock2 was ascertained by immunohistochemistry and the mRNA expression of TGF-β1 was ascertained by hybridization in situ. RESULTS: The pathological changes in the BUD and the DXM groups were alleviated when compared with the asthma group. The total cell number and the percentage of eosinophil (EOS), polymorphonuclear leukocytes (PMN) and lymphocytes (Lym) in BALF in the asthma group were significantly higher than those in the control group (P<0.01). The percentage of macrophage (Mф) in the asthma group was significantly lower than that in the control group (P<0.01). The total cell number and the percentage of EOS and Lym in BALF in the DXM and the BUD groups decreased, while the percentage of Mф increased significantly compared with those in the asthma group (P<0.01). The Rock2 and TGF-β1 mRNA expression in lung tissues in the asthma group increased significantly compared with those in the control, BUD and DXM groups, while there were no significant differences in the Rock2 expression and TGF-β1 mRNA expression between the DXM or BUD group and the control group. CONCLUSIONS: The expression of Rock2 and TGF-β1 mRNA in lung tissues is increased in rats with acute asthma. Glucocorticoids can significantly decrease the expression of Rock2 and TGF-β1 in lung tissues, thus alleviates airway inflammation.［Chin J Contemp Pediatr, 2010, 12 (11):877-881］