实用医学杂志
實用醫學雜誌
실용의학잡지
THE JOURNAL OF PRACTICAL MEDICINE
2015年
7期
1102-1106
,共5页
孙光曦%范理佩%石向华%李民%赵明
孫光晞%範理珮%石嚮華%李民%趙明
손광희%범리패%석향화%리민%조명
肾间质纤维化%脑肠肽%转化生长因子β1%Smad3%细胞凋亡
腎間質纖維化%腦腸肽%轉化生長因子β1%Smad3%細胞凋亡
신간질섬유화%뇌장태%전화생장인자β1%Smad3%세포조망
Renal interstitial fibrosis%Ghrelin%Transforming growth factor beta1%Smad3%Apoptosis
目的：研究脑肠肽对肾间质纤维化及肾细胞凋亡的改善作用及其作用机制。方法：将雄性Sprague-Dawley（SD）大鼠随机分为4组，假手术组＋盐水或脑肠肽治疗组，模型组＋盐水或脑肠肽治疗组。对模型组大鼠行左侧输尿管结扎术建立单侧输尿管梗阻（UUO）动物模型。术后7 d和14 d分批处死大鼠，留取梗阻侧肾组织行Masson染色以观察各组大鼠肾组织病理改变，通过免疫组化分析α平滑肌肌动蛋白（α-SMA）、转化生长因子β1（TGF-β1）、磷酸化的 Smad3（p-Smad3）的水平蛋白表达，用 realtime-PCR（RT-PCR）法检测α-SMA、TGF-β1的mRNA表达水平。用TUNEL染色法标记凋亡肾脏细胞。结果：脑肠肽通过减少胶原产生，抑制细胞外基质沉积和减少α-SMA 蛋白表达改善肾脏纤维化。同时，脑肠肽通过阻断 TGF-β1／Smad3信号通路，抑制肌成纤维细胞聚集。另外，脑肠肽改善UUO诱导肾小管细胞凋亡。结论：脑肠肽可以减少UUO诱导的肾脏纤维化、改善肾细胞凋亡，有望成为治疗梗阻性肾病肾脏纤维化的药物。
目的：研究腦腸肽對腎間質纖維化及腎細胞凋亡的改善作用及其作用機製。方法：將雄性Sprague-Dawley（SD）大鼠隨機分為4組，假手術組＋鹽水或腦腸肽治療組，模型組＋鹽水或腦腸肽治療組。對模型組大鼠行左側輸尿管結扎術建立單側輸尿管梗阻（UUO）動物模型。術後7 d和14 d分批處死大鼠，留取梗阻側腎組織行Masson染色以觀察各組大鼠腎組織病理改變，通過免疫組化分析α平滑肌肌動蛋白（α-SMA）、轉化生長因子β1（TGF-β1）、燐痠化的 Smad3（p-Smad3）的水平蛋白錶達，用 realtime-PCR（RT-PCR）法檢測α-SMA、TGF-β1的mRNA錶達水平。用TUNEL染色法標記凋亡腎髒細胞。結果：腦腸肽通過減少膠原產生，抑製細胞外基質沉積和減少α-SMA 蛋白錶達改善腎髒纖維化。同時，腦腸肽通過阻斷 TGF-β1／Smad3信號通路，抑製肌成纖維細胞聚集。另外，腦腸肽改善UUO誘導腎小管細胞凋亡。結論：腦腸肽可以減少UUO誘導的腎髒纖維化、改善腎細胞凋亡，有望成為治療梗阻性腎病腎髒纖維化的藥物。
목적：연구뇌장태대신간질섬유화급신세포조망적개선작용급기작용궤제。방법：장웅성Sprague-Dawley（SD）대서수궤분위4조，가수술조＋염수혹뇌장태치료조，모형조＋염수혹뇌장태치료조。대모형조대서행좌측수뇨관결찰술건립단측수뇨관경조（UUO）동물모형。술후7 d화14 d분비처사대서，류취경조측신조직행Masson염색이관찰각조대서신조직병리개변，통과면역조화분석α평활기기동단백（α-SMA）、전화생장인자β1（TGF-β1）、린산화적 Smad3（p-Smad3）적수평단백표체，용 realtime-PCR（RT-PCR）법검측α-SMA、TGF-β1적mRNA표체수평。용TUNEL염색법표기조망신장세포。결과：뇌장태통과감소효원산생，억제세포외기질침적화감소α-SMA 단백표체개선신장섬유화。동시，뇌장태통과조단 TGF-β1／Smad3신호통로，억제기성섬유세포취집。령외，뇌장태개선UUO유도신소관세포조망。결론：뇌장태가이감소UUO유도적신장섬유화、개선신세포조망，유망성위치료경조성신병신장섬유화적약물。
Objective To investigate the effect and underlying mechanisms of ghrelin in a rat model of renal fibrosis. Methods Male Sprague-Dawley rats were divided into 4 groups , including sham operation +saline or brain gut peptide treatment group , model + saline or brain gut peptide treatment group. Unilateral ureteral obstruction (UUO) was established by left ureteral ligation. 7 days and 14 days after operation, the rats were sacrificed , while the kidney tissue of obstruction side was harvested for pathlogical changes through Masson coloration. Expression of α-smooth muscle actin (α-SMA), transforming growth factor beta1 (TGF-β1) and phosphorylated Smad3 (p-Smad3) in renal tissues were analyzed through immunohistochemistry. Expression of α-SMA and TGF-β1 mRNA was detected by real-time-PCR. Apoptosis kidneys cells were marked with TUNEL. Results Ghrelin inhibited renal fibrosis by reducing the production of collagen , restraining extracellular matrix (ECM) deposition and decreasing the expression of α-SMA. Meanwhile, ghrelin inhibited the accumulation of myofibroblasts by blocking the transforming growth factor-β1/Smad3 (TGF-β1/Smad3) signaling pathway. Moreover, ghrelin could attenuate renal tubular cell apoptosis induced by UUO injury. Conclusion Ghrelin can reduce renal fibrosis and renal cell apoptosis induced by UUO , demonstrating that ghrelin is a potent antifibrotic agent that may have therapeutic potential for patients with obstructive nephropathy.
