重组人生长激素对败血症大鼠肠粘膜屏障功能保护作用的机制研究  

Studies of the Possible Mechanisms for Protective Effects of Recombinant Human Growth Hormone on Intestinal Mucosa Barrier in Rat Sepsis

作　　者：黄英[1] 易成[2] 龙洋[3] 赵秋玲[4] 江从勋[5] 崔勇霞[2] 贺荣华[1] 王树人[1] 

机构地区：[1]四川大学华西基础医学与法医学院病理生理学教研室,成都610041 [2]四川大学华西医院化疗科 [3]四川大学华西医院内分泌实验室 [4]四川大学华西公共卫生学院营养与食品卫生学教研室 [5]四川大学华西基础医学与法医学院机能室

出　　处：《四川大学学报（医学版）》2006年第1期10-13,共4页Journal of Sichuan University(Medical Sciences)

基　　金：四川省科技厅应用基础项目(03JY029-072-1)资助

摘　　要：目的观察重组人生长激素(RHGH)对败血症大鼠肠粘膜屏障功能的保护作用并探讨其可能的作用机制。方法采用腹腔注射E.COLI复制大鼠败血症模型。42只健康雌性SD大鼠随机分为正常对照组(C组)、败血症组(S组)及RHGH治疗组(T组),S组及T组又依观察时点再分为1D、3D两个亚组(T1D,T3D,S1D,S3D)。应用RT-PCR、免疫组化、放射免疫等方法,动态观测肝组织IGF-1MRNA表达情况、肠粘膜BCL-2蛋白表达水平及细菌移位、血浆生长激素(GH)及胰岛素样生长因子-1(IGF-1)水平及肠道形态等指标的变化情况。结果1RHGH能明显减轻败血症大鼠肠粘膜结构损伤,减轻肠道细菌移位。2T组大鼠肠粘膜BCL-2表达水平(T1D:2441±117;T3D:3628±235)明显高于S组水平(S1D:321±36;S3D:1873±57)(P<0.01)。3T组大鼠血浆GH水平〔T1D:(1.28±0.24)ΜG/L;T3D:(2.14±0.48)ΜG/L〕显著高于S组水平〔S1D:(0.74±0.12)ΜG/L;S3D:(0.60±0.18)ΜG/L〕(P<0.01)。4T组大鼠血浆IGF-1水平〔T1D:(168.94±65.67)ΜG/L;T3D:(201.56±64.98)ΜG/L〕明显高于S组水平〔S1D:(116.72±13.96)ΜG/L;S3D:(107.50±23.53)ΜG/L〕(P<0.05)。5T组大鼠肝IGF-1MRNA表达水平〔T1D:(0.98±0.20);T3D:(1.76±0.17)〕显著高于S组水平〔S1D:(0.38±0.09);S3D:(0.46±0.10)〕(P<0.01)。结论RHGH可能通过抑制肠粘膜上皮细胞凋亡及GH/IGF-1的作用来维护败血症大鼠肠粘膜屏障功能。Objective To investigate the protective effects of recombinant human growth hormone （rhGH） on intestinal mucosal barrier in rat sepsis and explore its possible mechanisms. Methods E. coli was injected intraperitoneally to produce rats sepsis models. Forty-two female SD rats were randomly divided into the control group （group C）, sepsis group （group S） and treatment group （groupT）. Group S and group T were further divided into 1 d and 3 d subgroups（T1d,T3d,S1d,S3d）, respectively. The expression of IGF-1 mRNA in liver, expression of Bcl-2 protein in intestine, bacteria translocation, the levels of growth hormone（GH） and insulin-like growth factor-1 （IGF-1） in plasma, and the histological appearance of intestine were determined dynamically by means of RT-PCR, radioimmunoassay, immunohistochemical staining and other corresponding methods, respectively. Results ①rhGH could significantly attenuate intestinal mucosal injuries and ameliorate bacteria translocation on sepsis rats. ② The levels of Bcl-2 protein expression in intestine in group T （T1d：2441 ±-117; TSd. 3628±235） were obviously higher than those of group S （S1d：321±36;S3d：1873±57）（P〈0. 01）. ③ The plasma levels of GH in group T （T1d：1.28±0.24μg/L;T3d ：2.14±0. 48μg/L） increased markedly than those of group S（S1d：0. 74±0.12μg/L;S3d：0. 60±0.18μg/L） （P〈0. 01）.④ The plasma levels of IGF-1 in group T （T1d.168.94±65.67μg/L;T3d：201.56±64. 98μg/L） elevated significantly than those of group S （S1d,116.72 ±13.96 μg/L;S3d,107.50±23.53μg/L） （P〈0. 05）. ⑤The levels of liver IGF-1 mRNA in group T （T1d,0. 98 ±0. 20：T3d：1.76±0. 17） were significantly higher than those in group S （S1d：0. 38±0. 09;S3d：0. 46±0. 10） （P 〈0. 01）. Conclusion rhGH conferred protective efficacy in maintaining the integrity of intestinal mucosal barrier against sepsis in rat. The possible mechanisms might involve the rhGH-diminished apoptosis of intestinal mucosa c

关 键 词：肠粘膜屏障 生长激素 败血症 胰岛素样生长因子-1 Bcl-2 

分 类 号：R965[医药卫生—药理学]