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首页> 外文期刊>Vascular pharmacology >A combination of Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, improved renal microvascular insufficiency in 5/6 nephrectomized rats
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A combination of Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, improved renal microvascular insufficiency in 5/6 nephrectomized rats

机译：结合中草药黄芪变种。 mongholicus和Angelica sinensis改善了5/6肾切除大鼠的肾微血管功能不全

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摘要

Chronic renal ischemia and hypoxia in the tubulointerstitium are involved in the mechanisms of progressive chronic kidney disease. Previous studies showed that the decoction of a combination of two Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis (A & A) has antifibrotic effects through multiple pathways in different animal models. In this study, remnant kidney model was employed to investigate whether A & A affect the expression of VEGF, the density of the renal microvasculature and thus alleviate the renal injury. Rats were divided randomly into four groups: sham group (N=31), 5/6 Nx group (5/ 6 nephrectomy, N=43), A & A treated group (A & A group, N=40, A & A12 g/kg/d po), enalapril treated group (Ena group, N=56, enalapril 4 mg/kg/d po). Rats from each group were sacrificed at the 2th, 4th, 8th and 12th weeks respectively after surgery and treatment The 24 h urinary protein excretion, serum creatinine (Scr) and urea were measured. The collagen IV (COL-IV), fibronectin (FN), aminopeptidase P (APP) and VEGF were stained using immunohistochemistry. The COL-IV, FN and APP were semi-quantitatively analyzed. Peritubular capillary density in the cortical interstitial area was quantified. The level of VEGF was assayed by ELISA. The results revealed that Scr, urea and urinary protein excretion remained constant at each time point in sham group. Compared to sham group, 5/6 Nx group was shown severe glomerulosclerosis, tubulointerstitial lesions and vascular damage, as well as higher level of Scr from the 2nd week (72.3+5.2 vs. 48.6?6 umol/L, P<0.05) to the 12th week (71.9+8.0 vs. 55.7?5 umol/L, p<0.05). Although there was no significant difference in Scr level after treatment of enalapril or A & A (P> 0.05), kidney damage was alleviated at the 8th and the 12th week in the two treatment groups (P<0.05, vs. 5/6 Nx group). The urinary protein excretion of 5/6 Nx group was significantly increased from the 4th week, it was 1.5,2.4 and 3.8 fold of that of sham group at the 4th, 8th and 12th week, respectively. Compared to 5/6 Nx group, proteinuria was decreased by enalapril to 59%, 33% at 8th and 12th week. After A & A administration, urinary protein excretion decreased to 66%. 56%, 75%, 55% of 5/6 Nx group at the 2nd, 4th, 8th and 12th, respectively (p<0.05). Compared with sham group, there was increased expression of FN and COL-IV in rats with 5/6 Nx. After A & A or enalapril administration, the expression of FN and COL-IV was significantly decreased compared with that in the 5/6 Nx group at 8th and 12th week (P<0.05). On the other hand, the capillary density was decreased at the 8th and 12th week in 5/6 Nx rats (P<0.01). In A & A-treated group, similarly with enalapril group, the amount of APP-positive glomerular capillary increased by 36% (P<0.01), and the peritubular capillary density was increased 94% at 8th week and 52% at 12th week compared with 5/6 Nx group (P<0.05). The renal level of VEGF was decreased in 5/6 Nx rats, but increased at the 8th and 12th week in A & A group (p<0.05, vs. 5/6 Nx group). In conclusion, A & A has renoprotective effects by suppression of extra cellular matrix deposition in 5/6 Nx rat The renoprotective effects may be associated with reduction of proteinuria, up-regulation of VEGF which may reduce the loss of capillaries and improve microstructure dysfunction.
机译：肾小管间质的慢性肾脏缺血和缺氧与进行性慢性肾脏疾病的机制有关。先前的研究表明，两种中草药黄芪的水煎汤合用。 Mongholicus和Angelica sinensis（A＆A）在不同的动物模型中通过多种途径具有抗纤维化作用。在这项研究中，采用残余肾脏模型来研究A和A是否会影响VEGF的表达，肾脏微脉管系统的密度，从而减轻肾脏损伤。大鼠随机分为四组：假手术组（N = 31），5/6 Nx组（5/6肾切除术，N = 43），A和A治疗组（A和A组，N = 40，A和A12 g / kg / d po），依那普利治疗组（Ena组，N = 56，依那普利4 mg / kg / d po）。分别在手术和治疗后第2、4、8和12周处死每组大鼠。测量24 h尿蛋白排泄，血清肌酐（Scr）和尿素。使用免疫组织化学法对胶原蛋白IV（COL-IV），纤连蛋白（FN），氨肽酶P（APP）和VEGF染色。对COL-IV，FN和APP进行了半定量分析。定量皮层间质区域的毛细血管密度。通过ELISA测定VEGF的水平。结果表明，假手术组各时间点的Scr，尿素和尿蛋白排泄量均保持恒定。与假手术组相比，从第2周开始，5/6 Nx组显示出严重的肾小球硬化，肾小管间质病变和血管损伤，以及较高的Scr水平（72.3 + 5.2 vs. 48.6？6 umol / L，P <0.05）第12周（71.9 + 8.0 vs. 55.7？5 umol / L，p <0.05）。尽管依那普利或A＆A治疗后Scr水平无显着差异（P> 0.05），但两个治疗组在第8周和第12周肾脏损害得到缓解（P <0.05，而5/6 Nx组）。从第4周开始，5/6 Nx组的尿蛋白排泄量显着增加，在第4，第8和第12周分别为假组的1.5、2.4和3.8倍。与5/6 Nx组相比，依那普利将蛋白尿减少至59％，第8周和第12周减少33％。 A＆A给药后，尿蛋白排泄降低到66％。 5/6 Nx组分别在第二，第四，第八和第十二位分别占56％，75％，55％（p <0.05）。与假手术组相比，在5/6 Nx的大鼠中FN和COL-IV的表达增加。 A，A，依那普利给药后第8、12周，FN和COL-IV的表达较5/6 Nx组明显降低（P <0.05）。另一方面，在5/6 Nx大鼠的第8周和第12周，毛细血管密度降低（P <0.01）。与依那普利组相似，在A＆A治疗组中，APP阳性肾小球毛细血管数量增加了36％（P <0.01），而第8周和第12周的肾小管毛细血管密度增加了94％和52％ 5/6 Nx组（P <0.05）。 5/6 Nx大鼠肾脏的VEGF水平降低，而A和A组在第8周和第12周时，肾脏的VEGF水平升高（p <0.05，而5/6 Nx组）。总之，A和A通过抑制5/6 Nx大鼠细胞内额外的细胞基质沉积而具有肾脏保护作用。肾脏保护作用可能与蛋白尿的减少，VEGF的上调有关，这可以减少毛细血管的丢失并改善微结构功能障碍。

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