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目的:观察抗肺癌合剂对荷瘤小鼠基底膜与细胞外间质的影响。方法:采用C57BL/6小鼠50只,雌雄各半,每只小鼠右侧腋窝皮下接种Lewis肺癌瘤细胞悬液0.2mL,24h后随机分为生理盐水组、模型对照组、CTX组和抗肺癌合剂组,以1.2mg/kg的抗肺癌合剂灌胃,生理盐水组、模型对照组予以等量生理盐水灌胃,每日1次,连续14天;CTX组予以20mg/kg腹腔注射,隔日1次,共给药6次。每天观察动物的一般情况,隔日称重,并观察各组小鼠皮下结节情况;给药结束24h后处死所有动物,处死前,各组小鼠行眼球取血,测血透明质酸、胶原蛋白-Ⅳ;处死剥离肿瘤组织,对接种部位肿瘤组织进行FN和LN免疫组织化学染色,采用图像分析技术检测各组肿瘤组织FN和LN阳性表达的积分光密度。结果:模型对照组Lewis荷瘤小鼠血清中HA及ColⅣ含量较正常小鼠显著增高(P<0.01);抗肺癌合剂组能显著降低Lewis荷瘤小鼠血清中HA及ColⅣ含量,与模型对照组比较(P<0.01);而CTX对Lewis荷瘤小鼠血清中HA及ColⅣ含量有显著降低作用;与生理盐水组比较(P<0.01);对HA及ColⅣ未显示出明显的影响。结论:抗肺癌合剂能抑制Lewis肺癌小鼠肿瘤生长和自发肺转移;能降低Lewis肺癌小鼠血清中HA和ColⅣ含量;能使FN在Lewis肺癌小鼠肿瘤周围脂肪组织、肿瘤包膜、血管壁及癌巢间呈断线状或连续线状表达。LN在模型组及CTX组中瘤细胞胞浆中有较高的表达,而抗肺癌合剂可显著降低其表达,显示抗肺癌合剂与CTX具有不同的作用机制。
Objective: To observe the effect of anti-lung cancer mixture on the basement membrane and extracellular matrix of tumor-bearing mice. METHODS: Fifty C57BL/6 mice were enrolled and divided into two groups: male and female, each mouse was inoculated subcutaneously with 0.2 mL Lewis lung cancer cell subcutaneously in the right armpits. After 24 hours, the mice were randomly divided into normal saline group, model control group, CTX group and antibiotics. In lung cancer mixture group, 1.2 mg/kg anti-lung cancer mixture was intragastrically administered, normal saline group and model control group were intragastrically administrated with equal volume of saline once a day for 14 consecutive days; CTX group was given intraperitoneally with 20 mg/kg every other day. Once, a total of 6 doses were administered. Observe the general condition of the animals every day, weigh them every other day and observe the subcutaneous nodules in each group. All animals are sacrificed 24 hours after the end of administration. Before the mice are sacrificed, blood is collected from the eyeballs of each group to measure blood hyaluronic acid and collagen. Protein-IV was sacrificed and the tumor tissue was removed. The tumor tissues at the inoculation site were stained with FN and LN immunohistochemistry. The integrated optical densities of FN and LN positive expression in the tumor tissues of each group were detected by image analysis technique. Results: The levels of HA and Col IV in serum of Lewis tumor-bearing mice in the model control group were significantly higher than those in normal mice (P<0.01). Anti-lung cancer mixture can significantly reduce the serum HA and Col IV in Lewis tumor-bearing mice. Compared with group (P<0.01), CTX had a significant decrease in HA and Col IV contents in serum of Lewis tumor-bearing mice; it was compared with saline group (P<0.01); it had no obvious effect on HA and ColIV. Conclusion: Anti-lung cancer mixture can inhibit tumor growth and spontaneous lung metastasis in Lewis lung cancer mice; it can reduce the serum HA and Col IV levels in Lewis lung cancer mice; and it can make FN in tumor surrounding acinar tissue, tumor capsule, and blood vessel wall in Lewis lung cancer mice. And between the cancer nests showed broken line or continuous linear expression. LN was highly expressed in the cytoplasm of tumor cells in the model group and CTX group, while anti-lung cancer mixture could significantly reduce its expression, indicating that the anti-lung cancer mixture has a different mechanism of action with CTX.