| ObjectiveTo investigate the remodeling of intrarenal small arteries(IRSAs)in diabetic spontaneously hypertensive rats(DSHR) and to study the effect of telmisartan on vascular remodeling . MethodsForty 12-week-old male SHRs were randomized to SHR group,DSHR group, telmisartan low dose(TelL) group,telmisartan high dose(TelH) group.Twenty age and sex matched 12-week-old male Wistar Kyoto rats were randomized to control group (WKY )and diabetic group (DWKY). TelL,TelH,DSHR and DWKY was induced by a single intraperitoneal injection of STZ .TelL and TelH group received different dosage of telmisartan intragastric administration respectively. AT the end of 8 weeks,all the rats were anesthetized,and left kidneys were excised and fixd in 10% neutral formalin. Morphological characteristics were evaluated with HE, Sirius - red, elasticity fibrin and collagen fibrin double staining (P/VB)。The IRSAs were divided into 3groups accoding to the external diameters:20-49μm,50-99μm and 100-200μm..Wall area (WA),wall thickness (WT),internal diameter (ID) and WT/ID of IRSAs were assessed with the compute-assisted image analysis system. Immunohistochemistry staining was performed to lable macrophages, vascular smooth muscle cells and III collagen(COLⅢ) .The apoptosis and proliferation of intrarenal small arterial smooth muscle cells were detected by in situ end labeling technique (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining respectively.The integrated optical density(IOD)of COLⅢwere count by compute-assisted image analysis system and PI and AI were caculated to assess proliferation and apoptosis.Results 1.Compared with WKY group,VR occurred in DWKY,SHRand DSHR groups ,Presenting with higher WT and WT /ID ,decreased ID and increased WA(the group with exrennal diameter from 20 to 49μm was excluded.p<0.01,p<0.05) All the index were more distinguished in DSHR group..2.There were more cell nucleus in intrarenal small arterial media in DWKYgroup and SHR in the groups with the the external diameter from 50 to 200μm; Compared with DWKY group or SHR,the number of cell nucleus increased in DSHR(p<0.05).Immunohistochemistry showed that the proliferation index (PI) of intrarenal arterial media in group SHRand DWKY was strikingly higher than that in WKY and so was DSHR to SHR and DWKY.3.The apoptosis index (AI) of IRSAs media in group SHR was remarkably lower than that in WKY group(p<0.01); group DWKY was lower than that in group WKY(p<0.01).There were no difference between group DSHRand goup DWKY or SHR.4.There was a significant decrease in the number of renal glomerulus in group DWKY compared with group WKY (p<0.01).No difference can be found between group SHR and WKY. Compared with DWKYgroup,the number of Renal glomerulus deceased in DSHR group(p<0.05).5.The integrated optical density(IOD)of COLⅢnear the vascular including adventitia.of SHR and DWKYgroup was higher(p<0.05,p<0.01)than that of WKY..group,and so was DSHR than SHRand DWKY. (p<0.01).6.The number of macrophages near the intrarenal small arteries of group DWKY increased compared with that of group WKY(p<0.01).The amount of macrophages in SHR was higher than DWKY,so was DSHR than SHR(p<0.01)..7.There was no diffrence on SBP between TelH group and WKY,just as TelL group and SHR.Increase of WT,WA,WT/ID and proliferation can be lessened in treatment groups ,and the reduction of renal glomerulus can be inhibited.TelH group can exert these effctes more effectively.Conclusions1. Among the apparent IRSAs remodeling in DWKY,SHR and DSHR group,DSHR group was the most noticeable one.2. The cytological mechanisms of intrarenal small arteries (IRSAs) remodeling mainly involve the unbalance of proliferation and apoptosis and excessive deposition of COLⅢ.3. Telmisartan could significantly attenuate the IRSAs remodeling in DSHR The mechanisms may involve decreasing proliferation,promoting the balance of proliferation and apoptosis and other effect。...
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