Intravital imaging of adriamycin-induced renal pathology using two-photon microscopy and optical coherence tomography

Adriamycin(doxorubicin),a common cancer chemotherapeutic drug,can be used to induce a model of chronic progressive glomerular disease in rodents.In our studies,we evahuated renal changes in a rat model after Adriamydin injection using two photon microscopy(TPM),optical coherence tomography(OCT)and Doppler OCT(DOCT).Taking advantage of deep penetra-tion and fast scanning speed for three dimensional(3D)label-free imaging,OCT/DOCT system was able to reveal glomerular and tubular pathology noninvasively and in real time.By imaging renal pathology following the infusion of fAuorophore-labeled dextrans of different molecular weights,TPM can provide direct views of glomerular and tubular flow dynamics with the onset and progression of renal disease.Specifically,glomerular permeability and filtration,proximal and distal tubular flow dynamics can be revealed.6-8 weeks after injection of Adriamycin,TPM and OCT/DOCT imaging revealed glomerular sclerosis,compromised flow across the glomerular wall,tubular atrophy,tubular dilation,and variable intra-tubular flow dynamics.Our results indicate that TPM and OCT/DOCT provide real-time imaging of renal pathology in vivo that has not been previously available using conventional microscopic procedures.

脂肪酸通过固醇调节元件结合蛋白1诱导足细胞的损伤

目的:确定脂代谢和固醇调节元件结合蛋白在糖尿病和肥胖相关肾病和足细胞损伤发病机制中的重要作用,为白桦脂醇治疗糖尿病肾病提供理论依据。方法:游离脂肪酸250μm处理分化后的人足细胞48 h,检测足细胞脂滴形成和TLR2/TLR4mRNA和活化的SREBP1以及TLR4的蛋白表达情况以及炎性细胞因子IL-6的mRNA的表达;SREBP1c脂质体转染足细胞,检测足细胞脂滴形成和TLR4和IL-6的表达。结果:游离脂肪酸250μm作用足细胞24 h即诱导人足细胞凋亡,CARS成像显示足细胞脂滴增加,活化的SREBP1的65 kD部分表达增加,TLR2/TLR4的mRNA和TLR4的蛋白表达增加,IL-6的mRNA增加;SREBP1c转染足细胞后,足细胞内脂质合成明显增加,TLR4的蛋白表达上调,IL-6mRNA表达上调。结论:SREBP1表达上调促进足细胞脂质沉积,诱导TLR2/TLR4通路活化,炎性细胞因子IL-6合成增加。SREBP1在2型糖尿病和肥胖肾病足细胞损伤过程中发挥重要作用,为2型糖尿病肾病和肥胖性肾病提供新的治疗靶点。