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  

Effects of Huanshuai Oral Liquid in the Process of Hypoxia-Microvascular Waste-Renal Interstitial Fibrosis in Mice with Atherosclerosis Renal Artery Stenosis

作　　者：方吕贵[1] 饶向荣[1] 李深[1] 王丽[1] 卢建新[1] 吴玲艳[1,2] 刘畅[1] 

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]解放军第174医院,福建厦门361003

出　　处：《中国中医药信息杂志》2015年第1期53-57,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81141122)

摘　　要：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。Abstract. Objective To explore the mechanism of Huanshuai Oral Liquid in the process of hypoxia-microvascular waste-renal interstitial fibrosis in mice with atherosclerosis renal artery stenosis. Methods The atherosclerosis renal artery stenosis model was established on Apoe-/- mice by high fat feed and uninephrectomy. After 2 weeks of renal ablation, model mice were randomly divided into TCM group （Huanshuai Oral Liquid） and model group. C57BL/6J mice were taken as the blank group. The mice of TCM group received Huanshuai Oral Liquid 0.01 mL/（g· d） for gavage, while the blank group and the model group received normal saline 0.01 mL/（g· d） for gavage. Renal function, atherosclerosis and renal interstitial fibrosis were assessed in the 12th week after taking medicine via immunohistochemical method to detect the expressions of the collagen type IV, alpha smooth muscle actin （α-SMA） and Ⅷ factor related antigen （vWF）, and via RT-PCR to detect the expressions of HIF-1α and TGF-β. Results Compared with the blank group, the model group suffered severe renal artery stenosis and renal fibrosis, and the expressions of HIF-1α, TGF-β, collagen type Ⅳ and a-SMA significantly increased （P^0.05）, while the expression of vWF decreased （P 〈 0.05）. Compared with the model group, the expressions of HIF-1α, TGF-α, collagentype Ⅳ and α-SMA group, the expressions of HIF-1α, TGF-β, collagen type Ⅳ ana type Ⅳ and α-SMA significantly decreased in the TCM group （P〈0.05）, while the expression of vWF significantly increased （P〈0.05）. Conclusion Huanshuai Oral Liquid could significantly improve the renal function and the renal tubular-interstitial fibrosis. The mechanism might be associated with regulating the expressions of HIF-lα and TGF-β.

关 键 词：动脉粥样硬化性肾动脉狭窄 缓衰口服液 肾间质纤维化 低氧 小鼠 

分 类 号：R285.5[医药卫生—中药学]