CAJ | 학술논문

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ApoE-/-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 mL/(g?d)灌胃,空白组和模型组予0.01 mL/(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(vWF)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),vWF 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),vWF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。
목적：탐토완쇠구복액대동맥죽양경화성신동맥협착(ARAS)소서신장저양-미혈관황폐-신간질섬유화병리과정적영향궤제。방법통과대ApoE-/-소서위이고지사료,병행좌측신장절제술,건립ARAS동물모형。수술2주후,장모형소서수궤분위완쇠구복액조(중약조)、모형조,령설공백조(C57BL/6J소서)。중약조용완쇠구복액0.01 mL/(g?d)관위,공백조화모형조여0.01 mL/(g?d)생리염수관위。급약12주후,취재,검측신공능,Masson 염색관찰신간질섬유화정도,면역조화법검측각조소서신장Ⅳ형효원、α-평활기기동단백(α- SMA)、혈관성혈우병인자(vWF)적표체,RT-PCR검측저양유도인자-1α(HIF-1α)화전화생장인자-β(TGF-β)적표체정황。결과여공백조비교,모형조소서신공능불전명현,신동맥협착엄중,신간질섬유화명현,HIF-1α、TGF-β、Ⅳ형효원화α-SMA 표체명현증가(P＜0.05),vWF 표체명현감소(P＜0.05)；여모형조비교,중약조HIF-1α、TGF-β、Ⅳ형효원화α-SMA표체명현감소(P＜0.05),vWF표체명현증가(P＜0.05)。결론완쇠구복액대ARAS소서적신공능화신간질섬유화유명현개선작용,해작용가능여기대결혈성신장HIF-1α화TGF-β표체적억제유관。
Objective To explore the mechanism ofHuanshuai 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 receivedHuanshuai 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 typeⅣ, alpha smooth muscle actin (α-SMA) andⅧ factor related antigen (vWF), and via RT-PCR to detect the expressions of HIF-1α and TGF-β.ResultsCompared with the blank group, the model group suffered severe renal artery stenosis and renal fibrosis, and the expressions of HIF-1α, TGF-β, collagen typeⅣ andα-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-β, collagen typeⅣ andα-SMA group, the expressions of HIF-1α, TGF-β, collagen typeⅣ andα-SMA significantly decreased in the TCM group (P<0.05), while the expression of vWF significantly increased (P<0.05).ConclusionHuanshuai 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-1α and TGF-β.