基于肾络瘀阻研究益肾活血方对单侧输尿管结扎大鼠肾脏血管内皮生长因子和Notch信号通路的影响
기우신락어조연구익신활혈방대단측수뇨관결찰대서신장혈관내피생장인자화Notch신호통로적영향
Based on kidney vascular and network static blood obstruction to study influence of prescription for boosting kidney and promoting blood circulation (Yishen Huoxue) on kidney vascular endothelial growth factor and Notch signal pathway in rats with unilateral ureter ligation
  • 万方数据
    中国中西医结合急救杂志 중국중서의결합급구잡지
    Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
    2015年 6期 577-581 ,共5页

    钟建%赵宁博%刘朝业

    종건%조저박%류조업

    益肾活血方%血管新生%血管内皮生长因子%Notch 益腎活血方%血管新生%血管內皮生長因子%Notch
    익신활혈방%혈관신생%혈관내피생장인자%Notch
    Yishen Huoxue herb prescription%Angiogenesis%Vascular endothelial growth factor%Notch
    目的：观察益肾活血方对单侧输尿管结扎（UUO）大鼠血管内皮生长因子-2（VEGF-2）、Notch4表达水平的影响。方法选择雄性SD大鼠96只，按随机数字表法分为假手术组、UUO模型组、氯沙坦治疗组、益肾活血方治疗组，每组24只。采用UUO方法复制肾纤维化动物模型，氯沙坦组和益肾活血方组分别以氯沙坦、益肾活血方灌胃进行干预；假手术组仅分离单侧输尿管后行腹部缝合。分别于术后7、14、21 d取血，检测各组尿素氮（BUN）、血肌酐（SCr）水平的变化；采集肾脏标本，检测肾脏组织微血管密度（MVD）及VEGF-2、Notch4的蛋白表达水平。结果与UUO模型组比较，各治疗组BUN、SCr水平显著降低，差异有统计学意义（均P＜0.01）；益肾活血方组BUN、SCr水平略低于氯沙坦组，但差异无统计学意义（均P＞0.05）。假手术组大鼠各时间点肾组织VEGF-2、Notch4蛋白表达水平均在正常范围内；而UUO模型组大鼠肾组织VEGF-2、Notch4蛋白表达随时间延长呈轻度增加，肾脏MVD下降的程度则逐渐加重。两个给药组大鼠肾组织VEGF-2、Notch4蛋白表达均较模型组显著增加；VEGF-2（A值）以术后14 d表达最强（假手术组、模型组、益肾活血方组和氯沙坦组14 d时分别为0.18±0.09、4.73±0.72、7.27±1.35、8.11±1.64，21 d时分别为0.19±0.07、4.05±0.88、7.10±1.12、7.79±1.53），此后呈轻度下降趋势；Notch4（A值）以21 d表达最强（4个组分别为0.62±0.35、9.08±1.52、14.48±3.14、15.54±3.38，均P＜0.05）；MVD（个/mm2）下降的程度较模型组显著减轻（4个组7 d时分别为45.20±6.25、25.34±4.67、30.23±4.20、32.26±4.36，14 d时分别为46.07±6.22、20.06±3.98、26.88±4.36、26.95±4.11，21 d时分别为45.18±6.10、17.79±3.72、21.71±4.25、21.68±4.41，P＜0.01或P＜0.05）；益肾活血方组的数值与氯沙坦相近，两组比较无显著差异。结论中药益肾活血方对肾纤维化过程中的微血管损伤有明显改善作用，这可能与药物对VEGF和Notch信号级联通路调控作用有密切关系。
    목적：관찰익신활혈방대단측수뇨관결찰（UUO）대서혈관내피생장인자-2（VEGF-2）、Notch4표체수평적영향。방법선택웅성SD대서96지，안수궤수자표법분위가수술조、UUO모형조、록사탄치료조、익신활혈방치료조，매조24지。채용UUO방법복제신섬유화동물모형，록사탄조화익신활혈방조분별이록사탄、익신활혈방관위진행간예；가수술조부분리단측수뇨관후행복부봉합。분별우술후7、14、21 d취혈，검측각조뇨소담（BUN）、혈기항（SCr）수평적변화；채집신장표본，검측신장조직미혈관밀도（MVD）급VEGF-2、Notch4적단백표체수평。결과여UUO모형조비교，각치료조BUN、SCr수평현저강저，차이유통계학의의（균P＜0.01）；익신활혈방조BUN、SCr수평략저우록사탄조，단차이무통계학의의（균P＞0.05）。가수술조대서각시간점신조직VEGF-2、Notch4단백표체수평균재정상범위내；이UUO모형조대서신조직VEGF-2、Notch4단백표체수시간연장정경도증가，신장MVD하강적정도칙축점가중。량개급약조대서신조직VEGF-2、Notch4단백표체균교모형조현저증가；VEGF-2（A치）이술후14 d표체최강（가수술조、모형조、익신활혈방조화록사탄조14 d시분별위0.18±0.09、4.73±0.72、7.27±1.35、8.11±1.64，21 d시분별위0.19±0.07、4.05±0.88、7.10±1.12、7.79±1.53），차후정경도하강추세；Notch4（A치）이21 d표체최강（4개조분별위0.62±0.35、9.08±1.52、14.48±3.14、15.54±3.38，균P＜0.05）；MVD（개/mm2）하강적정도교모형조현저감경（4개조7 d시분별위45.20±6.25、25.34±4.67、30.23±4.20、32.26±4.36，14 d시분별위46.07±6.22、20.06±3.98、26.88±4.36、26.95±4.11，21 d시분별위45.18±6.10、17.79±3.72、21.71±4.25、21.68±4.41，P＜0.01혹P＜0.05）；익신활혈방조적수치여록사탄상근，량조비교무현저차이。결론중약익신활혈방대신섬유화과정중적미혈관손상유명현개선작용，저가능여약물대VEGF화Notch신호급련통로조공작용유밀절관계。
    Objective To observe the influence of Yishen Huoxue prescription on expressions of vascular endothelial growth factor-2 (VEGF-2) and Notch4 in rats with unilateral ureter obstruction (UUO).Methods Ninety-six male Sprague-Dawley (SD) rats were randomly divided into sham operation group, UUO model group, losartan group, and Yishen Huoxue group, with 24 rats in each group. The rat models of renal fibrosis were reproduced by using UUO method, and they were treated by Yishen Huoxue herb prescription or losartan intra-gastric administration respectively for therapeutic interference. In the sham operation group, simply the unilateral ureter was separated from the near-by tissues and then the abdomen incision was stitched. The blood was collected on 7, 14 and 21 days after operation for determination of blood urea nitrogen (BUN) and serum creatinine (SCr). Kidney tissues specimens were harvested, and microvessed desity (MVD), the protein expression levels of VEGF-2 and Notch4 in the kidney were detected. Results Compared with UUO model group, BUN and SCr in both treatment groups were significantly decreased with significant difference (allP < 0.01). BUN and SCr in Yishen Huoxue group were slightly lower than those in losartan group without significant difference (bothP >0.05). The expression levels of VEGF-2 and Notch4 in sham operation group at each time point were in normal range; with the time extension, the expressions of VEGF-2 and Notch 4 protein were slightly increased, and the descent degree of MVD in kidney was aggravated gradually in UUO model group. The VEGF-2 and Notch4 protein expressions in kidney tissues of the two treatment groups were significantly increased compared with those in model group, the expression of VEGF-2 (A value) reached the highest level on the 14th day after operation (VEGF-2 levels in sham operation, model, Yishen Huoxue Herb prescription and losartan groups were 0.18±0.09, 4.73±0.72, 7.27±1.35, 8.11±1.64 on the 14th day, and they were 0.19±0.07, 4.05±0.88, 7.10±1.12,7.79±1.53 on 21th day, respectively), later representing a tendency of slight decrease, and Notch4 protein expression (A value) peaked on the 21st day (0.62±0.35, 9.08±1.52, 14.48±3.14, 15.54±3.38 in above four groups, allP < 0.05). The degrees of decrease in renal MVD (microvessel/mm2) in the both treament groups was significantly less than that in model group (45.20±6.25, 25.34±4.67, 30.23±4.20, 32.26±4.36 on the 7th day, 46.07±6.22, 20.06±3.98, 26.88±4.36, 26.95±4.11 on the 14th day, 45.18±6.10, 17.79±3.72, 21.71±4.25, 21.68±4.41 on the 21st day in above four groups,P < 0.05 orP < 0.01). There were no statistically significant differences in the above values between Yishen Huoxue herb group and losartan group.Conclusion Traditional Chinese medicine "benefiting qi for activating blood circulation therapy (Yishen Huoxue herb prescription)" has obvious improving effect on the microvascular injury in the process of renal fibrosis that possibly is related closely to the drug regulation on VEGF/Notch signaling cascade.
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