不同药物对肾衰大鼠小肠黏膜血管内皮生长因子表达、微血管密度分布与肠道清除能力的影响

Effect of Different Drugs on VEGF Expression,Microvessel Density,and Intestinal Scavenging Ability in Rat Renal Failure Model

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 relationship between VEGF expression,microvessel density(MVD)of the kidney and intestinal scavenging ability in rat renal failure model.Methods:Fifty rats were randomly divided into 5groups(model group,sham operation group,indomethacin group,ligustrazine hydrochloride group and benazepril hydrochloridec group),and renal failure model was conducted by 5/6nephrectom.Rats were then given indomethacin,ligustrazine hydrochloride and benazepril hydrochloridec by gavage,respectively.Levelsof Cr and BUN in the blood and fecal,and VEGF expression and MVD distribution of glomerular were evaluated and analyzed.Results:1After 8weeks treatment,Cr and BUN in the blood and fecal in the model group,indomethacin group,ligustrazine hydrochloride group and benazepril hydrochloride group were higher than those in the sham operation group(P<0.05);blood and fecal Cr and BUN in the ligustrazine hydrochloride group and benazepril hydrochloride group were lower than those in the model of group,fecal BUN was higher than that in the model group(P<0.05);no statistical significance was shown in blood Cr and BUN between indomethacin group and model group(P>0.05),while fecal Cr and BUN of indomethacin group were significantly higher(P<0.05);compared with indomethacin group,Cr and BUN of the blood and fecal in the ligustrazine hydrochloride and benazepril hydrochloride groups were obviously lower(P<0.05);between benazepril hydrochloride group and ligustrazine hydrochloride group,there was also the significant differences in blood Cr and BUN,as well as fecal Cr(P<0.05).2Compared with the sham operation group,positive expression of VEGF and MVD in the other four groups was significantly decreased(P<0.05);compared with the model group,positive expression of VEGF and MVD in the ligustrazine hydrochloride group and benazepril hydrochloride group was remarkablely increased(P<0.05),but that in indomethacin group was decreased(P<0.05);the difference of VEGF expression in ligustrazine hydrochloride group and the group of benazepril hydrochloride compared with indomethacin group was statistically significant(P<0.05);there was statistical significance in the MVD expression between ligustrazine hydrochloride group and benazepril hydrochloride group(P<0.05),but no significant difference was found in VEGF expression(P>0.05);3 The Pearson correlation analysis showed that renal VEGF and MVD have significant correlation(r=0.845,P<0.05);4 The Pearson correlation analysis also showed that it was a negative correlation of VEGF and MVD in the renal with blood BUN,but a positive correlation with fecal Cr and BUN(P<0.05).Conclusion:Ligustrazine hydrochloride and benazepril hydrochloride might increase the VEGF expression and MVD of residual nephrons,promote intestinal clearance of BUN and Cr,and have protective effect on chronic renal failure;indomethacin could decrease expression of renal VEGF and MVD,which may aggravate kidney damage.