清肺化痰通络方对肺纤维化大鼠基质金属蛋白酶-2、基质金属蛋白酶-9表达的影响

Effect of Qingfei Huatan Tongluo Fang on the expression of MMP-2 and MMP-9 in rats with pulmonary fibrosis

目的探讨清肺化痰通络方对博莱霉素A5(BLMA5)所致肺纤维化大鼠的干预作用及可能机制。方法将Wistar大鼠随机分为对照组、模型组、干预组。模型组和干预组通过气管插管灌注BLMA5复制大鼠肺纤维化模型,对照组给予等量生理盐水气管灌注;对照组和模型组给予生理盐水灌胃,干预组给予清肺化痰通络方药物灌胃。灌胃后3、7、14、28 d分别处死大鼠,采用HE和Masson染色观察肺组织病理变化,免疫组化染色检测基质金属蛋白酶-2(MMP-2)、MMP-9在肺组织的表达水平。结果清肺化痰通络方能显著改善大鼠的一般身体状况,减轻肺泡炎及肺纤维化的程度。干预组和模型组肺内MMP-2表达在第14天达到高峰,MMP-9的表达在第7天达到高峰,且两组同时期MMP-2、MMP-9的表达均高于对照组(P<0.05);干预组MMP-2、MMP-9表达低于同时期模型组(P<0.01)。结论清肺化痰通络方可能通过抑制MMP-2、MMP-9在肺内的表达,对BLMA5致肺组织纤维化起到一定的防治作用。

Objective To discuss the preventive effect and possible mechanism of Qingfei Huatan Tongluo Fang on model rats with pulmonary fibrosis induced by bleomyein A5 （BLMA5）. Methods Wistar rats were randomly divided into the con- trol group, the model group and the intervention group. The rats in the model group and the intervention group were given BLMA5 though trachea eannula to establish pulmonary fibrosis model, the control group was given normal saline though trachea cannula; the control group and the model group were gastric lavaged by normal saline, intervention group was gas- tric lavaged by Qingfei Huatan Tongluo Fang. After gastric lavage of 3, 7, 14, 28 days, rats were killed respectively. The pathological changes of lung tissue were observed by HE and Masson staining, and the expression levels of matrix metallo- proteinase （MMP） -2 and MMP-9 in lung tissue were detected by immunohistochemical staining. Results The rats general physical condition could be significantly improved by the Qingfei Huatan Tongluo Fang, the pulmonary alveolitis and pul- monary fibrosis degree reduced also. The intervention group and the model group of intrapulmonary MMP-2 expression achieved the peak in the 14th day, but the expression of MMP-9 peaked at 7th days. The expression of MMP-2 and MMP-9 in both model group and intervention group were higher than the control group at the the same time （P 〈 0.05）; the MMP-2 and MMP-9 expression in the intervention group were lower than the model group at the same period （P 〈 O.O1）. Conclusion Qingfei Huatan Tongluo Fang has certain treatment effect on pulmonary fibrosis in the model rats in- duced by BLMA5, the mechanisms probably through inhibition of excessive expression of MMP-2 and MMP-9 in intrapul