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目的:观察“通利大肠”对慢性阻塞性肺疾病(COPD)模型大鼠肺组织的基质金属蛋白酶-9(MMP-9)、转化生长因子-β(TGF-β)蛋白表达和细胞信号转导分子Smad3mRNA,Smad7mRNA基因水平变化,从气道重构角度探讨COPD“从肠论治”的效应机制。方法:用气管注射脂多糖加熏香烟联合造模方法建立COPD大鼠模型,随机分为正常组、模型组、治肠组、治肺组及肺肠同治组。正常组、模型组灌胃10 mL.kg-1纯净水,各给药组灌胃相应中药(治肠组、治肺组、肺肠同治组的药量分别为1.50,4.25,5.75 g.kg-1),连续14 d。用免疫组化法测量肺组织中MMP-9,TGF-β蛋白阳性表达面积比率,用实时荧光定量PCR法测定肺组织Smad3和Smad7的mRNA水平。结果:①与正常组比较,模型组大鼠肺组织MMP-9和TGF-β表达增强,蛋白阳性面积比率值分别为1.231%和3.002%,Smad3mRNA水平升高至14.804,Smad7mRNA水平降低至0.2(P<0.01)。②与模型组比较,治肠组肺组织MMP-9,TGF-β分别为0.944%和1.989%,二者表达减少,Smad3mRNA水平降低,Smad7mRNA水平升高(P<0.05或P<0.01)。③与治肺组比较,肺肠同治组的肺组织TGF-β表达和Smad3mRNA水平减少,而Smad7mRNA水平升高至0.784(P<0.01),MMP-9的表达则有减少的趋势。结论:通利大肠或在治肺的基础上增加通利大肠,能抑制慢性阻塞性肺疾病模型大鼠的气道重构,从而减轻气道阻塞,改善通气障碍及肺功能,这可能是COPD“从肠论治”效应产生的作用环节之一。
OBJECTIVE: To observe the expression of matrix metalloproteinase-9 (MMP-9), transforming growth factor-β (TGF-β) in lung tissue of COPD rat model and the effect of “Tom Lee” The signal transduction molecules Smad3mRNA, Smad7mRNA gene level changes from the perspective of airway remodeling COPD “from the bowel governance ” effect mechanism. Methods: COPD rat models were established by tracheal injection of lipopolysaccharide plus cigarette smoking, and were randomly divided into normal group, model group, treatment of intestine group, treatment of lung group and lung intestine. Normal group and model group were fed with 10 mL.kg-1 purified water, and each administration group was given gavage of the corresponding traditional Chinese medicine (Zhigong group, Zhiji group and Zhigong group) with the doses of 1.50, 4.25 and 5.75 g.kg -1) for 14 days. The positive expression area of MMP-9 and TGF-βprotein in lung tissue was measured by immunohistochemistry, and the mRNA levels of Smad3 and Smad7 in lung tissue were detected by real-time fluorescence quantitative PCR. Results: ①Compared with the normal group, the expression of MMP-9 and TGF-β in the lung tissue of model group increased significantly, the positive rate of protein was 1.231% and 3.002%, the level of Smad3 mRNA increased to 14.804 and the level of Smad7 mRNA decreased to 0.2 P <0.01). ② Compared with the model group, the levels of MMP-9 and TGF-β in the lungs of the treatment group were 0.944% and 1.989%, respectively. The expressions of Smad3 mRNA and Smad3 mRNA were decreased (P <0.05 or P <0.01). ③Compared with the control lung group, the expression of TGF-β and Smad3 mRNA in the lung tissue of the lung-intestine group were decreased, but the level of Smad7 mRNA increased to 0.784 (P <0.01), while the expression of MMP-9 decreased. CONCLUSION: Tongliao intestine or Tongliao large intestine, based on the lung, can inhibit airway remodeling in rats with chronic obstructive pulmonary disease, thereby reducing airway obstruction, improving ventilation and pulmonary function, which may be COPD “From the treatment of bowel ” effect one of the links.