摘要
目的动态观察DAPT对Notch2/hes1信号通路在庆大霉素诱导肾损伤及修复过程中表达的影响。方法72只成熟大鼠随机分成空白组(生理盐水,3 ml·kg-1·d-1,腹腔注射,持继10 d)、DAPT组(DAPT,5 mg·kg-1·d-1,连用5 d、停用2 d后再用3 d;庆大霉素,120 mg·kg-1·d-1,腹腔注射,持继10 d)和庆大霉素组(庆大霉素,120 mg·kg-1·d-1,腹腔注射,持继10 d)。应用光镜、电镜观察肾小管损伤情况。应用免疫印迹蛋白、实时定量PCR观察大鼠Notch2/hes1信号途径在造模后1 d、14 d、28 d肾脏的动态表达情况。结果肾脏病理切片示:在第1、14 d,与空白组相比,模型组、DAPT组造成的肾脏损伤程度有所不同;在第1、14 d,与模型组相比,DAPT组造成的肾脏损伤程度明显减轻;在28 d,模型组和DAPT组肾小管基本恢复正常。免疫印迹蛋白、RT-PCR示:在第1、14 d,与空白组相比,模型组和DAPT组Notch2/hes1的表达明显增高(P<0.05);在第1、14 d,与模型组相比,DAPT组Notch2/hes1的表达明显减少(P<0.05);在第28 d,各组表达无明显差异(P>0.05)。结论 Notch2/hes1信号通路可能是庆大霉素诱导肾损伤及修复过程中的重要角色之一,DAPT可能通过抑制Notch2/hes1信号通路减轻肾脏损伤并促进肾小管上皮细胞修复。
Objective To dynamically observe effect of DAPT on expression of Notch2/hes1 in gentamicin-induced renal injury and re-pair process. Methods Seventy-two mature rats were randomly divided into the normal group( saline,intraperitoneal injection,once daily, held following the ten days),the DAPT group(DAPT 5 mg/(kg·d),intraperitoneal injection,held following the five days,continuous three days after stop two days. Gen 120 mg/kg,once daily,intraperitoneal injection,continuous ten days)and gentamicin group( Gen 120 mg/kg, once daily,intraperitoneal injection,continuous ten days). The renal damage was observed by light microscopy and electron microscopy. By west-ern-blotting,real-time quantitative PCR,observed expression of the Notch2/hes1 at 1,14,28 day post-modeling. Results Renal biopsy showed:at 1,14 day,the degree of kidney damage is different in the DAPT group and model group compared with the normal group;at 1,14 day,the degree of kidney damage is obvious mitigation in the DAPT group compared with the model group;at 28 day,tubular back to normal in DAPT and gentamicin groups. Western blot protein,RT-PCR shows:at 1,14 day,the level of Notch2/hes1 increased significantly in model group and DAPT group( P <0. 05)compared with the normal group. At 1,14 day,the level of Notch2/hes1 significantly in DAPT group( P <0. 05)compared with the model group. At 28 day,there is no significant difference( P >0. 05). Conclusion Notch2/hes1 signaling pathways may be one of the important role in the gentamicin-induced renal injury and repair process. DAPT may be go through inhibit Notch2/hes1 signa-ling pathways to reduce renal injury and promote tubular epithelial cell repair.
出处
《临床和实验医学杂志》
2015年第17期1401-1405,共5页
Journal of Clinical and Experimental Medicine
基金
国家临床重点专科建设项目资助