当归补血颗粒早期干预结缔组织生长因子防治高血压肾损害及肾血管病变

摘要

Objective:To investigate the effect of early drug intervention of Danggui Buxue granules expression of CTGF in Spontaneously Hypertensive RatS(SHR)on renal interstitial fibrosis and renal vascular lesion.Method:SHR were randomly divided into early group and late group.Early group and late group were then divided into danggui buxue granules group(DG group) and normal saline group (NS group).Early group was choosed 8 weeks old SHR and late group of 12 weeks old SHR. Normal group was choosed WKY rats at the same age in early and late groups. The rats were treated with DG 6 g/(kg·d)by gastric gavage in DG group and equivalent normal saline by gastric gabage in NS group and WKY rats,the rats were sacrificed at 28 weeks old.Serum creatinine,urea nitrogen and urinary β2 microglobulin were detected.Pathological changes of the renal tissue were observed by HE staining;the mRNA expression of CTGF was detected by real-time PCR, and the protein expression of CTGF was detected by Western Blot.Result:Compared with NS group, early DG group serum creatinine,urea nitrogen ,urinary β2 microglobulin ,the renal interstitial damage index, the degree of vasular lesions ,the expression of CTGF mRNA and CTGF were significantly reduced,the differences were statistically significant(P<0.05). In late group, compared with NS group,DG group of urinary β2 microglobulin,the renal interstitial damage index, the degree of vasular lesions ,the expression of CTGF mRNA and CTGF reduced, the difference was statistically significant(P<0.01).The effection in early group was better than late group,DG was no effect on blood pression in SHR(P>0.05).Conclusion:Early intervention by DG can significantly attenuates renal interstitial fibrosis and renal vascular lesions in SHR by suppressing the expression of CTGF,the effection was no relationship with blood flow dynamics.%目的：探讨当归补血颗粒早期干预结缔组织生长因子（CTGF）在防治高血压肾损害肾间质纤维化及肾血管病变中的意义。方法：自发性高血压大鼠（SHR），根据用药时间分为早期组和晚期组，早期组选用8周龄SHR，晚期组选用12周龄SHR，并设置同龄WKY大鼠为正常对照组。早期组包括当归补血颗粒治疗组（DG组）和生理盐水对照组（NS组），晚期组包括当归补血颗粒治疗组（GD组）和生理盐水对照组（NS组）。早期组以当归补血颗粒6 g/（kg·d）灌胃，直至28周龄；晚期组以同样剂量当归补血颗粒灌胃，直至28周龄。尾动脉无创测压法观察各组大鼠血压情况，生化方法测定治疗前后各组大鼠的血肌酐、尿素氮和尿β2微球蛋白水平，组织病理学染色观察大鼠肾间质纤维化及肾血管病变情况，Real-time PCR和Western Blot检测各组大鼠的CTGF表达。结果：早期组DG治疗后SHR血肌酐、尿素氮、尿β2 MG、肾间质纤维化指数、血管病变评分、CTGF mRNA和蛋白表达均较NS组明显降低，差异有统计学意义（P<0.01）。晚期组治疗后，DG组尿β2 MG、肾间质纤维化指数、血管病变评分、CTGF mRNA和蛋白表达与NS组比较均下降，差异有统计学意义（P<0.05），早期组的治疗效果优于晚期组；当归补血颗粒治疗对SHR血压无影响（P>0.05）。结论：当归补血颗粒早期干预治疗能明显改善高血压肾损害大鼠肾功能和肾间质纤维化病变及血管病变程度，这一作用与干预肾组织CTGF表达相关，与血流动力学无关。