防纤汤对放射性肺炎大鼠的影响及作用机制

目的 研究防纤汤对放射性肺炎大鼠肺部组织病理、肺表面活性物质结合蛋白和炎症因子的影响,探讨防纤汤治疗放射性肺炎的疗效和作用机制。 方法 将90只SPF级雄性SD大鼠随机分空白组、模型组和3个治疗组(低剂量组、中剂量组和高剂量组),利用6 mV X射线对治疗组、模型组大鼠全胸照射,总剂量20 Gy,进行放射性肺炎大鼠造模处理,治疗组予灌胃防纤汤,模型组及空白组予灌胃等量生理盐水。照射后第1天灌胃用药直至照射后6周,照射后第2、4、8周每组随机取6只大鼠取材,在HE染色光镜下观察肺组织病理形态学变化,免疫组化法检测白细胞介素-3(IL-3)、白细胞介素-6(IL-6)、白细胞介素-7(IL-7)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、C 反应蛋白(CRP)、肺表面活性物质结合蛋白(SP-A、SP-D)水平,并作相关性分析。 结果 与模型组相比,治疗组大鼠肺组织充血及水肿较轻或无,炎症细胞浸润性少或无,间质内存在较少或无胶原纤维增生。与空白组比较,模型组、治疗组IL-3、IL-6、IL-7、TNF-α、TGF-β、CRP水平均明显升高(中剂量治疗4周,P值分别为0.012、0.033、0.027、0.018、0.024、0.009),SP-A、SP-D水平均明显降低(中剂量治疗4周,P值分别为0.004、0.005);与模型组比较,治疗组IL-3、IL-6、IL-7、TNF-α、TGF-β、CRP水平均明显降低(P<0.05),SP-A、SP-D水平均明显升高(P<0.05)。相关性结果分析发现,IL-6与SP-A、SP-D呈强负相关性,IL-3、IL-7与SP-A、SP-D呈负相关性,TNF-α、TGF-β与SP-A、SP-D呈弱正相关性。不同剂量的治疗组对大鼠肺组织病理和所检测的体液因子的影响具有剂量相关性。 结论 防纤汤改善放射性肺损伤炎性程度的疗效明确。SP-A、SP-D的变化与IL-3、IL-6、IL-7、TNF-α、TGF-β具有相关性,推测防纤汤的作用机制是通过上调SP-A、SP-D水平,抑制炎症因子IL-3、IL-6、IL-7的释放。

Effect of Fangxian Decoction on rats with radiation pneumonia and its mechanism

Objective To study the effect of Fangxian Decoction on lung tissue pathology, lung surface active substance binding protein and inflammatory factors of rats with radiation pneumonia, and to explore the efficacy and mechanism of Fangxian Decoction in the treatment of radiation pneumonia. Methods Ninety SPF male SD rats were randomly divided into blank group, model group and 3 treatment groups(low-dose group, middle-dose group and high-dose group), and 6mV X-rays with the total dose of being 20 Gy were used to irradiate the whole chest of rats in the treatment groups and model group to build the model of the rats with radiation pneumonia. The treatment groups were given Fangxian Decoction by gavage, and the model group and the blank group were given the same amount of normal saline by gavage. Gavage medication on the first day of irradiation until 6 weeks after irradiation. Six rats were selected from each group in the second, fourth, and eighth week after irradiation to observe the pathological changes of lung tissue under HE staining light microscope, detect the levels of interleukin-3(IL-3), interleukin-6(IL-6), interleukin-7(IL-7), tumor necrosis factor-α(TNF-α), transforming growth factor-β(TGF-β), C-reactive protein(CRP), and lung surfactant binding protein(SP-A, SP-D)by immunohistochemical method, and make correlation analysis. Results Compared with the model group, the rats in the treatment groups had less or no pulmonary congestion and edema, inflammatory cell infiltration, and collagen fiber proliferation in the interstitium. Compared with the blank group, the IL-3, IL-6, IL-7, TNF-α, TGF-β, and CRP levels in the model group and treatment groups were significantly increased(medium-dose treatment for 4 weeks, P values were 0.012, 0.033, 0.027, 0.018, 0.024, and 0.009, respectively), SP-A and SP-D levels were significantly reduced(middle dose treatment for 4 weeks, P values were 0.004 and 0.005, respectively). Compared with the model group, IL-3, IL-6, IL-7, TNF-α, TGF-β, CRP levels were significantly reduced(P<0.05), and SP-A and SP-D levels were significantly increased(P<0.05)in treatment groups. Analysis of the correlation results showed that IL-6 was strongly negatively correlated with SP-A and SP-D, IL-3 and IL-7 were negatively correlated with SP-A and SP-D, and TNF-α and TGF-β were weakly positively correlated with SP-A and SP-D. The effects of different doses of treatment groups on the pathology of rat lung tissue and the detected humoral factors were dose-dependent. Conclusion Fangxian Decoction has a clear effect on improving the inflammatory degree of radiation lung injury. The changes of SP-A and SP-D are related to IL-3, IL-6, IL-7, TNF-α and TGF-β. It is speculated that the mechanism of Fangxian Decoction is through up-regulation of SP-A and SP-D levels and inhibiting the release of inflammatory factors IL-3, IL-6, and IL-7.