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目的:探讨肾衰状态下不同药物对模型大鼠血管内皮生长因子(VEGF)表达和微血管密度(MVD)分布与肠道清除能力的影响。方法:50只大鼠随机分为5组,以5/6肾脏切除法制备肾衰模型,并分别采用吲哚美辛、盐酸川芎嗪和盐酸贝那普利进行灌胃,比较血、粪肌酐(Cr)、尿素氮(BUN)和肾小球VEGF和MVD变化。结果:1灌胃8周后,模型组、吲哚美辛组、盐酸川芎嗪组和盐酸贝那普利组血、Cr、BUN均高于假手术组,差异具有统计学意义(P<0.05);盐酸川芎嗪组和盐酸贝那普利组血Cr、BUN,粪Cr均低于模型组,粪BUN高于模型组,差异具有统计学意义(P<0.05);吲哚美辛组血Cr、BUN与模型组差异无统计学意义(P>0.05),粪Cr、BUN与模型组差异具有统计学意义(P<0.05);盐酸川芎嗪和盐酸贝那普利血Cr、粪Cr、BUN与吲哚美辛组差异具有统计学意义(P<0.05);盐酸贝那普利组与盐酸川芎嗪组血Cr、BUN,粪Cr差异具有统计学意义(P<0.05);2与假手术组相比,其他各组VEGF和MVD阳性表达均明显减弱(P<0.05);与模型组相比,盐酸川芎嗪组和盐酸贝那普利组VEGF和MVD阳性表达增强(P<0.05),吲哚美辛组表达降低(P<0.05);盐酸川芎嗪组和盐酸贝那普利组与吲哚美辛组组VEGF表达差异有统计学意义(P<0.05);盐酸川芎嗪组和盐酸贝那普利组MVD差异具有统计学意义(P<0.05),但VEGF差异无统计学意义(P>0.05);3经Pearson相关性分析发现,肾脏VEGF和MVD具有显著相关性(r=0.845,P<0.05);4经Pearson相关性分析发现,肾脏VEGF和MVD与血BUN具有负性相关关系,与粪Cr、粪BUN具有正性相关关系(P<0.05)。结论:盐酸川芎嗪和盐酸贝那普利能够上调小肠黏膜VEGF和MVD表达,促进BUN和Cr的肠道清除,对慢性肾衰具有保护作用;吲哚美辛可以降低VEGF和MVD表达,有可能加重肾脏损伤。
Objective: To investigate the effects of different drugs on the expression of vascular endothelial growth factor (VEGF), microvessel density (MVD) and intestinal clearance in rats with renal failure. Methods: Fifty rats were randomly divided into five groups. The model of renal failure was established by 5/6 nephrectomy. Indomethacin, ligustrazine hydrochloride and benazepril hydrochloride were intragastrically administered respectively. Blood, creatinine (Cr), urea nitrogen (BUN) and glomerular VEGF and MVD changes. Results: After 8 weeks of gavage, blood, Cr and BUN in the model group, indomethacin group, ligustrazine hydrochloride group and benazepril hydrochloride group were significantly higher than those in the sham operation group (P <0.05) ); Ligustrazine hydrochloride group and benazepril group blood Cr, BUN, excretion of Cr were lower than the model group, fecal BUN higher than the model group, the difference was statistically significant (P <0.05); indomethacin group blood There was no significant difference between Cr, BUN and model group (P> 0.05), but there was significant difference between Cr, BUN and model group (P <0.05); Ligustrazine hydrochloride and benazepril hydrochloride blood Cr, BUN and indometacin groups had statistical significance (P <0.05). The blood levels of Cr, BUN and Cr in blood of benazepril hydrochloride group and ligustrazine hydrochloride group had statistical significance (P <0.05) Compared with the model group, the expression of VEGF and MVD in ligustrazine hydrochloride group and benazepril hydrochloride group were significantly increased (P <0.05) , And indomethacin group (P <0.05). The expression of VEGF in ligustrazine hydrochloride group and benazepril hydrochloride group and indomethacin group was significantly different (P <0.05), and that in ligustrazine hydrochloride group and Benazepril hydrochloride group M (P <0.05) .3 The Pearson correlation analysis showed that there was a significant correlation between the expression of VEGF and MVD (r = 0.845, P <0.05), but there was no significant difference between the two groups ; 4 Pearson correlation analysis showed that there was a negative correlation between the expression of VEGF and MVD in kidney and BUN in blood and positive correlation with excretion of Cr and fecal BUN (P <0.05). CONCLUSION: Tetramethylpyrazine hydrochloride and benazepril hydrochloride can up-regulate the expression of VEGF and MVD in intestinal mucosa, promote the intestinal clearance of BUN and Cr, and have a protective effect on chronic renal failure. Indometacin can reduce the expression of VEGF and MVD, which may be Increased kidney damage.