| Objective: To study the mark proteins of renal tubular epithelial myofibroblast transdifferentiation(TEMT) in progressive interstitial fibrosis in type2 diabetic rats, revealed the pathology of occurrence and development of renal tubular lesion and tubulointerstitial fibrosis in diabetic nephropathy(DN),and the effects of rosiglitazone to it and renal function. Methods: Making 2 type diabetic rats mode by given high-sugar and high-fat diets, associating injection of small count streptozotocin(STZ) in abdominal cavity, to observe fast blood sugar(FBG), insulin(Ins), TG, TC, Ccr, Uaer and pathological changes in control, diabetic, and rosiglitazone-treated groups successively, and to detect the expressions of a-SMA, Vim, CK18, TGF-β1 in proximal tubular epithelial cells by immunohistochemistry, to detect a-SMA, TGF-β1's expressions by flow cytometry. Results: 1 Symptom and sign: the diabetic rats showed the symptoms of polyuria, polydipsia, polyphagia, after injection of STZ 1 to 2 days. At week 12, those symptoms were obvious, as the progression of DN, which became serious. At week 24, the diabetic rats'spirits dispirited, hairs dimmed, the behaiviors reduced. But the weights of diabetic rats did not low in the whole progression, the rosiglitazone-treated group was similar with the diabetic group in symptom and sign. 2 Biochemical examination: At week 12, the FBG, Ins, TG, Ccr, Uaer of diabetic group more significantly increased, than normal group, Ccr decreased(P<0.05),which were aggravated progressively, to week 24, the Ins, TG, Uaer more increased than at week 24 and TC also increased. But FBG was in a high level constantly. The FBG of the rosiglitazone-treated group, comparing to diabetic group, which did not significantly decreased(P>0.05), but Ins and TC largly decreased, Uaer increased.3 Pathological changes: Light microscopy: at week 12, comparing to normal group, in diabetic group, a few of the tubules atrophy or dilataltion and the tubular epithelia cells were swelling, and light fatty degeneration in the cytoplasm. At week 24, the tubules significantly dilatalted, tubular epithelia cells were more swelling or atrophy than at week 12. Some of the tubular basement membrane thickness, and glycogen granules in the cytoplasm (PAS staining). Electron microscopy: tubular epithelia cells swelling severely, some of the tubular basement membrane thickness significantly; a lots bound of collagen fibers among the tubules. In rosiglitazone-treated group, those pathological changes lightened, between the normal group and diabetic group.4 The mark proteins and cytokine about TEMT: Immunohistochemical staining: comparing to normal group, in the diabetic rats the expressions of a-SMA,Vim,TGF-β1 enhanced and depend to time. Expression of CK decreased. In rosiglitazone group, expressions of those were all between the normal group and the diabetic group.The detections of a-SMA and TGF-β1 by Flow cell technic are coincidence with results of immunohistochemistry.5 correlation between a-SMA, TGF-β1 and TG,TC,Uaer,Ccr: the increase of a-SMA,TGF-β1 were significantly positive correlation with TG, TC, Uaer and negative correlation with Ccr.Conclusion: In the present study, making type 2 diabetic rat mode by given the high-sugar and high-lipid diets associating injection of small count STZ, FBG,Ins,TG,TC,Uaer all significantly increased in diabetic group, and as the progression of DN, they were more severe. That process were coincidence in pathophysiological process type 2 diabetes and the pathological changes of kidney. The pathological observation show, there is really the TEMT during the process of DN, and TGF-β1 is a key cytokine in TEMT. It is paralleled with the level of the renal function, illustrating that TEMT plays a very important role in the process of DN. Treating with rosiglitazone not only can relieve the insulin resistance, correct the disturbance of lipo-metabolism, decrease the Uaer, also can relieve the TEMT, delay the interstitial fibrosis... |
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