Lu Xiao-Dong, Pang Li-Jian, Wang Lin-Lin, Nan Ming-Hua, Ma Zhi
Department of Respiratory Diseases, the Second Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang 110034, Liaoning Province, China.
Zhong Xi Yi Jie He Xue Bao. 2010 Oct;8(10):961-7. doi: 10.3736/jcim20101008.
To observe the expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rats with pulmonary fibrosis (PF) induced by bleomycin, and to explore the mechanisms of Shenlong Decoction in preventing and treating PF.
A total of 230 Wistar rats were divided into normal control group, untreated group, prednisone group, and low-, medium- and high-dose Shenlong Decoction groups. Wistar rats were intratracheally injected with bleomycin to induce PF. From the 2nd day, rats in the normal control and untreated groups were lavaged with normal saline (NS), and rats in the other groups were lavaged with prepared Shenlong Decoction by the same amount. Hematoxylin-eosin (HE) staining and Masson staining were used to observe pathological changes in lung tissue at different time points, and to evaluate whether the model was successfully induced. Expressions of MMP-2 and TIMP-1 mRNAs in rats' lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR).
Expressions of MMP-2 and TIMP-1 mRNAs in lung tissue of rats were observed from all groups at each time point. In comparison with the normal control group, on the 7th day, the transcription levels of MMP-2 and TIMP-1 mRNAs, especially the former, of the untreated group increased significantly (P<0.05 or P<0.01). On the 14th day, the transcription levels of MMP-2 and TIMP-1 mRNAs kept rising, especially the latter (P<0.05 or P<0.01). On the 28th day, the transcription level of MMP-2 decreased a little, while the transcription level of TIMP-1 mRNA did not stop increasing (P<0.05 or P<0.01). Compared with the untreated group, decrease of the transcription levels of MMP-2 and TIMP-1 mRNAs were observed in the treatment groups, especially the former, and this effect continued to the 28th day with the medium-dose Shenlong Decoction group decreasing most obviously (P<0.05 or P<0.01).
Shenlong Decoction may inhibit the expression of MMP-2 mRNA by up-regulating the expression of TIMP-1 mRNA so as to slow the progression of PF.
观察博来霉素诱导的肺纤维化（PF）大鼠模型中基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-1（TIMP-1）的表达情况，探讨神龙汤防治PF的作用机制。
将230只Wistar大鼠分为正常对照组、未治疗组、泼尼松组、神龙汤低、中、高剂量组。采用气管内注射博来霉素诱导Wistar大鼠发生PF。从第2天起，正常对照组和未治疗组大鼠用生理盐水（NS）灌胃，其他组大鼠用等量制备好的神龙汤灌胃。采用苏木精-伊红（HE）染色和Masson染色观察不同时间点肺组织的病理变化，评估模型是否成功建立。采用逆转录-聚合酶链反应（RT-PCR）检测大鼠肺组织中MMP-2和TIMP-1 mRNA的表达。
各时间点各组大鼠肺组织均观察到MMP-2和TIMP-1 mRNA的表达。与正常对照组相比，第7天时，未治疗组MMP-2和TIMP-1 mRNA的转录水平显著升高，尤其是前者（P<0.05或P<0.01）。第14天时，MMP-2和TIMP-1 mRNA的转录水平持续上升，尤其是后者（P<0.05或P<0.01）。第28天时，MMP-2的转录水平略有下降，而TIMP-1 mRNA的转录水平仍持续升高（P<0.05或P<0.01）。与未治疗组相比，各治疗组MMP-2和TIMP-1 mRNA的转录水平均降低，尤其是前者，且中剂量神龙汤组至第28天时降低最为明显（P<0.05或P<0.01）。
神龙汤可能通过上调TIMP-1 mRNA的表达抑制MMP-2 mRNA的表达，从而减缓PF的进展。
