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目的探讨大承气颗粒对多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)大鼠小肠平滑肌细胞(smooth muscle cell,SMC)凋亡的干预作用及其机制。方法健康成年Wistar大鼠100只,随机分为对照组(20只)、模型组(40只)和大承气颗粒组(中药组,40只)。模型组和中药组大鼠予腹腔注射大肠希氏菌(E.coli)混悬液,建立细菌性腹膜炎致MODS模型,中药组造模前2天给予大承气颗粒(1mL/100g)灌胃,2次/天,连续3天。造模24h后取存活大鼠的上段小肠组织,分别进行末端脱氧核苷酸转移酶介导的dUTP缺口标记技术(terminal-deoxynucleotidyl transferase mediated nick end labeling,TUNEL)和免疫组织化学染色,观察大承气颗粒干预前后MODS大鼠小肠SMC的凋亡数量及线粒体凋亡信号途径B细胞淋巴瘤/白血病-2(B cell lymphoma/lewkmia-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2associated X protein,Bax)、细胞色素C(cytochrome c,Cyt c)蛋白表达的变化。结果与对照组比较,模型组小肠SMC凋亡数量、Bax、Cyt c蛋白表达明显升高(P<0.01),Bcl-2蛋白表达明显减少(P<0.01)。与模型组比较,中药组小肠SMC凋亡数量、Bax、Cyt c蛋白表达明显降低(P<0.01),Bcl-2蛋白表达明显升高(P<0.01)。结论大承气颗粒可以通过抑制小肠SMC线粒体凋亡途径的激活,抑制SMC的凋亡,从而促进MODS大鼠胃肠运动功能的恢复。
Objective To investigate the effect and mechanism of Dachengqi Granule on the apoptosis of SMC in multiple organ dysfunction syndrome (MODS) rats. Methods One hundred healthy adult Wistar rats were randomly divided into control group (n = 20), model group (n = 40) and Dachengqi granule group (n = 40). The rats in model group and traditional Chinese medicine group were intraperitoneally injected with E.coli suspension to establish bacterial peritonitis-induced MODS model. The Chinese medicine group was administered with Dachengqi Granule (1mL / 100g) orally , 2 times / day for 3 consecutive days. Twenty-four hours after modeling, the upper intestine tissue of the surviving rats was taken and subjected to terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and immunohistochemical staining respectively. The number of apoptotic SMC and the signal pathways of mitochondria apoptosis in MODS rats before and after gas-particle intervention B cell lymphoma / leukemia-2 (Bcl-2), Bcl-2 related protein B (Bcl- 2associated X protein (Bax) and cytochrome c (Cyt c) protein expression. Results Compared with the control group, the apoptotic number of SMC, the expression of Bax and Cyt c in the model group were significantly increased (P <0.01), while the expression of Bcl-2 protein in the model group was significantly decreased (P <0.01). Compared with the model group, the apoptosis of small intestine, the expression of Bax and Cyt c, and the expression of Bcl-2 in the SMC group were significantly decreased (P <0.01). Conclusion Dachengqi granule can inhibit the SMC apoptosis by inhibiting the mitochondrial apoptotic pathway of SMC in the small intestine and thus promote the recovery of gastrointestinal motility in MODS rats.