目的:研究中药干预对热毒血瘀证荷瘤小鼠肺组织中基质金属蛋白酶(MMP)及细胞外信号调节激酶(ERK)的影响。方法:用LPS尾静脉和腹腔注射建立热毒血瘀证模型,C26皮下注射建立荷瘤模型,设空白对照组,单纯荷瘤组,复合模型对照组,复合模型高、中、低剂量组,以血府逐瘀汤合犀角地黄汤为干预因素,4周后取肺组织进行相关指标检测。结果:与复合模型对照组比较,复合模型高、中、低剂量组MMP-2、p ERK1/2表达均增高(P<0.05,P<0.01);复合模型高、中剂量组MMP-12表达下降(P<0.01,P<0.05)。结论:证实了热毒血瘀状态可影响结肠癌荷瘤小鼠肺组织中基质金属蛋白酶及p ERK1/2的表达;低、中、高剂量的中药干预,能不同程度上调MMP-2、ERK1/2的表达,下调MMP-12的表达,可能进一步引起肿瘤肺转移的发生。
Objective: To explore the expressions of MMPs and ERK in pulmonary tissue of mice with colorectal cancer suffering from noxious heat with blood stasis syndrome, analyzing the effects of microenvironment in lung tissue though the condition of the noxious heat with blood stasis and activating blood and resolving stasis. Methods: Establishing model by LPS of tail intravenous injection and peritoneal injection and C26 tumor cells subcutaneous injection, mice were randomly divided into 6 groups, respectively called blank control group(group A), tumor-bearing mice group(group B), control group with tumor(group C), tumor-bearing mice group with high dose herb medicine(group D), tumor-bearing mice group with middle dose herb medicine(group E), tumor-bearing mice group with low dose herb medicine(group F). Xuefu Zhuyu Decoction and Xijiao Dihuang Decoction, exhibited as interventional factor for 4weeks. The lung tissue was fixed for Western blot, immunohistochemistry and HE staining. Results: Compared with the group C, MMP-2 in group D, E, F were increased(P<0.05); Compared with the group C, p ERK1/2 in group D,E,F were increased(P<0.01); Compared with the group C, MMP-12 in group D were decreased(P<0.01), MMP-12 in group E were decreased(P<0.05). Conclusion: The study confirmed mice with colorectal cancer suffering from noxious heat with blood stasis syndrome can have influence of the expression of MMPs and ERK in mice with colorectal carcinoma with noxious heat with blood stasis syndrome, with concrete expression to the down-regulation of MMP-2, p ERK1/2 and the up-regulation of MMP-12. Given different dosage of Xijiao Dihuang Decoction as the treatment, respectively degree of down-regulation of MMP-12 as well as up-regulation of MMP-2 and ERK1/2, which may be the reason for the induces the development and metastasis of tumor.
China Journal of Traditional Chinese Medicine and Pharmacy