加味四君子汤对H22荷瘤小鼠移植瘤血管生成的影响

Effect of Modified Si Junzitang on Angiogenesis of H22 Tumor-bearing Mice

目的:观察加味四君子汤对H22荷瘤小鼠移植瘤血管生成的影响,并探讨其机制。方法:小鼠成瘤实验观察加味四君子汤对荷瘤小鼠的抑瘤和对癌周血管生长的影响。苏木素-伊红(HE)染色及免疫组化(IHC)检测荷瘤小鼠移植瘤中血管分布水平和血管内皮标记物(CD31)的表达水平。逆转录-聚合酶链式反应(RT-PCR)检测肿瘤组织血管内皮生长因子(VEGF),血管内皮生长因子受体2(VEGFR2),肿瘤坏死因子-α(TNF-α) mRNA表达。结果:加味四君子汤低、中、高剂量组(ig,11. 83,23. 66,47. 32 mg·kg^(-1)·d^(-1))抑瘤率分别达到29. 97%,59. 80%,82. 34%。与模型组相比,加味四君子汤中、高剂量组的平均瘤重明显降低(P <0. 05)。通过观察癌周血管数及形态发现,加味四君子汤中、高剂量组癌周血管数较模型组有所减少(P <0. 05),且血管管腔较窄。HE染色显示加味四君子汤中、高剂量组移植瘤中的血管分布均少于模型组。免疫组化显示加味四君子汤各剂量组的CD31阳性表达量均低于模型组(P <0. 01)。RT-PCR结果显示加味四君子汤中、高剂量组移植瘤VEGF,VEGFR2,TNF-αmRNA表达量均低于模型组(P <0. 01)。结论:加味四君子汤能够抑制H22荷瘤小鼠肿瘤生长,并抑制移植瘤血管新生,这可能与降低TNF-α,VEGF,VEGFR2的表达水平有关。

Objective:To investigate the effect of modified Si Junzitang on angiogenesis in transplanted tumor of H22 tumor-bearing mice.Method:The effect of modified Si Junzitang on tumor inhibition and growth of peripheral blood vessels in tumor-bearing mice was observed by tumorigenesis experiment in mice.Hematoxylineosin(HE)staining and immunohistochemistry(IHC)were used to detect the distribution of blood vessels and the expression of vascular endothelial markers(CD31)in tumor-bearing mice.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR2)and tumor necrosis factor-α(TNF-α)in tumor tissue.Result:The inhibition rates of modified Sijunzi Tang in low-dose group(ig,11.83 mg·kg-1·d-1),middle-dose group(ig,23.66 mg·kg-1·d-1)and high-dose group(ig,47.32 mg·kg-1·d-1)were 29.97%,59.80%and 82.34%,respectively.Compared with the model group,the average tumor weight was lower in middle and highdose groups,with statistically significant differences(P<0.05).Through the observation of the number and morphology of pericardial vessels,the number of pericytes in middle and high-dose modified Sijunzitang groups was reduced compared with the model group(P<0.05),and the vascular lumen was narrow.HE staining showed that the distribution of blood vessels in middle and high-dose modified Si Junzitang groups was less than that of the model group.IHC showed that the positive expression of CD31 in each dose modified Si Junzitang group was lower than that in the model group(P<0.01).RT-PCR showed that the mRNA expressions of VEGF,VEGFR2 and TNF-αin middle and high-dose modified Si Junzitang groups were lower than those in the model group(P<0.01).Conclusion:Modified Si Junzitang can inhibit the tumor growth of H22 tumor-bearing mice and the angiogenesis of transplanted tumors,which may be related to the reduction of TNF-α,VEGF and VEGFR2 expression levels.