调补肺肾三法对COPD大鼠T淋巴细胞亚群及CD4^+CD25^+的影响及远后效应

Influence and Long-term Effects of Three Methods for Regulating and Invigorating Fei-Shen on T Lymphocyte Subsets and CD4^+CD25^+ in COPD Rats

目的评价调补肺肾(补肺健脾、补肺益肾、益气滋肾)三法对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠T淋巴细胞亚群及CD4+CD25+的影响及远后效应。方法 120只大鼠随机分为对照组、模型组、补肺健脾组、补肺益肾组、益气滋肾组和氨茶碱组,每组20只。除对照组外,其余大鼠均采用香烟熏吸联合细菌感染法制备COPD模型,于第9周起3个中药组及氨茶碱组分别给予补肺健脾方、补肺益肾方、益气滋肾方及氨茶碱灌胃至第20周。分别于第20、32周观察肺组织病理、外周血和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4+/CD8+)及CD4+CD25+的变化。结果第20、32周时,模型组肺组织损伤明显,外周血和BALF中CD3+、CD4+、CD8+、CD4+CD25+水平较对照组明显降低(P<0.05,P<0.01),3个中药组及氨茶碱组上述指标较模型组升高(P<0.05,P<0.01);3个中药组外周血和BALF中CD3+、CD4+显著高于氨茶碱组(P<0.05,P<0.01);补肺健脾组外周血CD4+较补肺益肾组、益气滋肾组升高(P<0.01)。第20周时,补肺健脾组较氨茶碱组升高(P<0.01);3个中药组CD4+水平较氨茶碱组明显升高(P<0.05,P<0.01)。第32周时,3个中药组和氨茶碱组CD4+/CD8+水平较模型组升高(P<0.05);补肺健脾组和补肺益肾组CD4+较氨茶碱组升高(P<0.05,P<0.01)。与第20周比较,补肺健脾组第32周BALF中CD4+/CD8+显著升高(P<0.05),益气滋肾组外周血和BALF中CD4+CD25+显著降低(P<0.05)。结论调补肺肾三法治疗COPD的疗效和远后效应机制可能与调节T淋巴细胞亚群及CD4+CD25+水平有关,其中补肺健脾方在调节外周血和BALF中CD4+、CD4+/CD8+方面疗效突出。

Objective To evaluate the therapeutic and long-term effects of three methods for regulating and invigorating Fei-Shen E reinforcing Fei and invigorating Pi （RFIP）, reinforcing Fei and invig- orating Shen （RFIS）, benefiting qi and nourishing Shen （BQNS）I on T lymphocyte subsets and CD4＋ CD25 ＋ in rats with chronic obstructive pulmonary disease （COPD）. Methods Totally 120 rats were ran- domly divided into the control group, the model group, the RFIP group, the RFIS group, the BQNS group, and the aminophyline group, 20 in each group. Except those in the control group, the rest rats were ex- posed to cigarette smoking and bacterial infection to prepare the COPD rat model. Rats in the RFIP group, the RFIS group, the BQNS group, and the aminophyline group were administrated with Bufei Jianpi Reci- pe, Bufei Yishen Recipe, Yiqi Zishen Recipe, and aminophyline from week 9 to 20. After rats were sacri- ficed at week 20 and 32, lung pathological impairments and the levels of T lymphocyte subsets （CD3 ＋CD4 ＋ , CD8 ＋ , CD4 ＋/CD8 ＋） and CD4 ＋CD25 ＋ in the peripheral blood and the bronchoalveolar lavage fluid （BALF） were detected. Results At week 20 and 32, the impairments in the lungs were obvious in rats of the model group, while the levels of CD3 ＋ , CD4 ＋ , CD8 ＋ , and CD4 ＋ CD25 ＋ were significantly lower in the peripheral blood and the BALF in the model group than in the controls group （P 〈0.05, P 〈0.01）, and they were higher in the four groups than in the model group （P 〈0.05, P 〈0.01 ）. However, the levels of CD3 ＋ and CD4 ＋ in the peripheral blood and the BALF were higher in the three TCM-treated groups than in the aminophylline group （P 〈0.05, P 〈0.01 ）. CD4 ＋ in the peripheral blood in the RFIP group was higher than in the RFIS group and the BQNS group （P 〈0.01）.At week 20, the ratio of CD4 ＋/CD8 ＋ was higher in the RFIP group than in the aminophylline group （P 〈0.01 ）. CD4 ＋ was higher in the three TCM-treated groups than in the aminophylline group （P 〈0.05, P 〈0.01 ）. At week 32, the ratio of CD4 ＋/CD8＋ in the three TCM-and aminophylline-treated groups was higher than that of the model group （P 〈0.05）. CD4 ＋ in the RFIP group and the RFIS group was higher than that of the aminophylline group （P 〈0.05, P 〈0.01 ）. Compared with that at week 20, the ratio of CD4 ＋/CD8 ＋ in the BALF group was significantly higher in the RFIP at week 32 （P 〈0.05）. The CD4 ＋CD25 ＋ levels in the peripheral blood and BALF of the BQNS group was significantly lower （P 〈0.05）. Conclusions The efficacy and long-term effects of three methods for regulating and invigorating Fei-Shen might be possibly associated with regulating T lymphocyte subsets （CD3 ＋ , CD4 ＋ , CD8 ＋ , CD4 ＋/CD8 ＋） and CD4 ＋CD25 ＋levels. Of them, RFIP showed significant effects in regulating CD4 ＋ and CD4 ＋/CD8 ＋ in the peripheral blood and BALF.