Effects of Huanshuai Recipe Oral Liquid (缓衰口服液) on Restructuring Glomerular Microvasculature and Expression of Vascular Endothelial Growth Factor in Subtotal Nephrectomized Rats

Objectives：To explore the effects and significance of Huanshuai Recipe Oral Liquid（缓衰口服液,HSR）,a formula with supplementing qi,nourishing blood and activating blood on restructuring glomerular microvasculature and expression of vascular endothelial growth factor（VEGF）in subtotal nephrectomized（SNX） rats.Methods：A total of 76 male Wistar rats were randomly divided into four groups：16 in the sham-operated group and fed with tap water 10 mL/kg per day; 20 in the model group were operated with 5/6 SNX and fed with tap water 10 mL/kg per day; 20 SNX rats in the HSR group were treated with HSR 10 mL/kg per day; 20 SNX rats in the losartan group were treated with losartan 40 mg/kg per day.Serum creatinine（SCr）and urinary protein excretion（Upro）were examined at the 2nd,4th,8th,and 12th weeks of the treatment,and the remnant kidneys were harvested.Changes in histological microstructure were evaluated using light microscopy,and the expression of VEGF was detected by using ELISA.Results：Upro,microvasculature injury and glomerulosclerosis were found to be alleviated in HSR and Losartan groups,respectively.The change of VEGF expression showed positive correlation with glomerular capillary area and peritubular capillary number（r=0.448,r=0.422,P〈0.01）, but negative correlation with that of SCr and Upro（r=-0.592,r=-0.481,P〈0.01）.Conclusions：HSR could regulate the VEGF expression,reduce the loss of microvasculature,which demonstrated similar renal protective effects to losartan in SNX rats.Examination of Chinese herbal medicine influence on VEGF signaling and restructuring renal microvasculature may elucidate the molecular mechanism of renal protection to a certain degree.

Effect of Huanshuai Recipe Oral Liquid (缓衰口服液) on Renal Dysfunction Progression in Patients with Atherosclerotic Renal Artery Stenosis

Objective： To investigate the effect of Huanshuai Recipe Oral Liquid （缓衰口服液, HSR） on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis （ARAS）. Methods： A total of 52 ARAS patients with the Chinese medicine （CM） syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group （36 cases） and the control group （16 cases）. Both groups received a basic treatment （high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.）. In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function （serum creatinine, blood urea nitrogen and uric acid） and blood lipids （cholesterol, triglycerides and low density lipoprotein） were examined monthly. The estimated glomerular filtration rate （eGFR） and CM syndrome score were compared between groups. Results： After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased （P〈0.05 or P〈0.01）, and the eGFR in the treatment group were significantly increased （P〈0.05）. Conclusion： HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

益肾缓衰方延缓慢性肾功能衰竭进展的作用

目的 :观察中药益肾缓衰方对慢性肾功能衰竭 (chronicrenalfailure,CRF)进展的作用。方法 :46例CRF患者分为两组 ,A组 (自身对照组 ) 1 8例治疗分为两个阶段 ,第一阶段先以低蛋白饮食及控制高血压治疗 ,第二阶段加用益肾缓衰方治疗 ;B组 2 8例 ,治疗方案与A组第二阶段相同。以计算血清肌酐倒数 (dl/mg)与时间 (月 )的直线回归斜率的方法评估慢性肾功能衰竭的进展速度。结果 :A组第一阶段血清肌酐倒数与时间的直线回归斜率均数为 -0 .0 1 0 4± 0 0 0 2 1 ,A组第二阶段斜率均数为 -0 0 0 3 4± 0 0 0 1 8,两者比较有显著性差异 (P <0 0 5 ) ;B组斜率均数为 -0 0 0 47± 0 0 0 2 0 ,与A组第一阶段比较有显著性差异 (P <0 0 5 )。结论 :在低蛋白饮食和控制高血压的基础上加用中药益肾缓衰方 ,可使慢性肾功能衰竭进展速度明显延缓。

缓衰口服液对动脉粥样硬化性肾动脉狭窄小鼠肾脏低氧-微血管荒废-肾间质纤维化的影响

目的探讨缓衰口服液对动脉粥样硬化性肾动脉狭窄(ARAS)小鼠肾脏低氧-微血管荒废-肾间质纤维化病理过程的影响机制。方法通过对Apo E-/-小鼠喂以高脂饲料,并行左侧肾脏切除术,建立ARAS动物模型。手术2周后,将模型小鼠随机分为缓衰口服液组(中药组)、模型组,另设空白组(C57BL/6J小鼠)。中药组用缓衰口服液0.01 m L/(g·d)灌胃,空白组和模型组予0.01 m L/(g·d)生理盐水灌胃。给药12周后,取材,检测肾功能,Masson染色观察肾间质纤维化程度,免疫组化法检测各组小鼠肾脏Ⅳ型胶原、α-平滑肌肌动蛋白(α-SMA)、血管性血友病因子(v WF)的表达,RT-PCR检测低氧诱导因子-1α(HIF-1α)和转化生长因子-β(TGF-β)的表达情况。结果与空白组比较,模型组小鼠肾功能不全明显,肾动脉狭窄严重,肾间质纤维化明显,HIF-1α、TGF-β、Ⅳ型胶原和α-SMA表达明显增加(P<0.05),v WF表达明显减少(P<0.05);与模型组比较,中药组HIF-1α、TGF-β、Ⅳ型胶原和α-SMA表达明显减少(P<0.05),v WF表达明显增加(P<0.05)。结论缓衰口服液对ARAS小鼠的肾功能和肾间质纤维化有明显改善作用,该作用可能与其对缺血性肾脏HIF-1α和TGF-β表达的抑制有关。

缓衰方对5/6肾切除大鼠细胞外基质的影响

目的:研究缓衰方对纤维连接蛋白(FN)、转化生长因子β_2(TGF-β_2)在5/6肾切除大鼠肾小球中的含量的影响。方法:Wistar 大鼠5/6肾切除造模,随机分为对照组、缓衰方组,观察实验开始、第6周及第12周血肌酐(SCr)、24 h 尿蛋白定量变化,以及免疫组化加图像分析检测 FN、TGF-β_2的相对含量。结果:动物经5/6肾切除后,SCr、24 h 尿蛋白定量增加,经缓衰方灌胃12周,SCr、24 h 尿蛋白定量减少,与对照组比较,差异有显著性(P<0.05);免疫组化显示,缓衰方组 FN、TGF-β_2的相对含量较对照组明显降低,两组比较,差异亦有显著性(P<0.05)。结论:缓衰方通过抑制过高 TGF-β_2水平,而减少细胞外基质成分 FN 在肾小球的积聚,延缓肾衰进展速度,保护残肾功能。