The Role Of Aquaporin-1 In Diabetic Nephropathy Conversion

Diabetes has become one of the main causes of increasing morbidity and mortality in the worldwide at present stage,diabetic kidney disease is a common cause of chronic renal function failure. The number of diabetics is increased gradually at present now. Therefore, to delay diabetes complications and to reduce the incidence rate of diabetic kidney becomes a hot spot in the field of medical research. The water channel protein was discovered at the end of the last century, which is located on the cell membrane protein, can control the access of water inside and outside the cell. Aquaporin-1(AQP1), distributed widely in the kidney, is mostly expressed in renal proximal tubule and Henle loop descending branch of the plasma membrane. It not only mediates renal water transportation and regulation, but also osmotic diuresis regulation of the water in diabetes. Therefore, we speculate that the structure and function of AQP1 may have a certain relationship with the occurrence of diabetic kidney disease. It can be found that the progress of some kidney diseases was related with AQP1 in many medical reports. Previous researches mostly focus on the relationship between AQP1 and renal pathophysiology and kidney tumor diseases, there have been a very few reports of whether AQP1 participating in the occurrence of diabetic nephropathy. In this study, we establishment the model of AQP1 knockout mice diabetes and wild type mice, and explore the AQP1 expression change on the effects of the development of diabetic nephropathy and the effect of intervention through comparing them, so as to understand how AQP1 works in the progress of diabetic nephropathy, providing a new method to delay the progress of diabetic nephropathy and the experimental data.Methods:First of all, 8-week-old AQP1 knockout mice and wild-type mice were divided into diabetic group and normal control group. Diabetic model mice were established by intraperitoneal injection of streptozotocin(50mg/kg/d)for 5 consecutive months. During this period, blood glucose, body weight, urine changes and so on are monitored, then the model mice were sacrificed. Renal pathology analysis and immunohistochemical examination and kidney tissue Western blot assay for the detection of inflammatory, fibrosis, antioxidant index were performed. Through comparing the difference of above indexes between wild-type and AQP1 knockout mice with diabetes, then we find that AQP1 may play a role in advances of diabetes and its kidney complications.Results:1. The general data is compared with the control group, mice of AQP1 knockout diabetes group and wild type diabetes group a significant rise in blood sugar levels, weight loss, kidney volume increase, but AQP1 knockout diabetes group and wild type diabetes group weight, blood sugar, kidney weight was no significant differences..2. The renal pathology in mice kidney tissue HE, PAS, MASSON staining showed that AQP1 knockout mice diabetes group are obvious pathological changes compared with the control group and wild type mice, characterized by glomerular volume slightly increased, mesangial cell proliferation and mesangial matrix increase.AQP1 knockout diabetes group compared with wild type diabetes mellitus group, pathological changes is heavier, a significant expansion of renal tubule.3. The AQP1 knockout mice diabetes rat and wild type diabetes rat urine albumin/uric creatinine ratio(ACR) are higher than the control group.Compared with wild type diabetes mellitus group, AQP1 knockout ACR diabetes group was obviously higher, the differences were statistically significant.4. The wild type mice model compared with wild in the control group, found that kidney AQP1 expression quantity increased.5. Wild type diabetes group and AQP1 knockout diabetes inflammation factor of TNF alpha, fibrosis factor TGF- beta and anti-oxidation factor SOD- 1 expression than the control group were significantly increased, it can be found that AQP1 knockout diabetes is slightly higher than wild type diabetes group by comparing with the two groups,, but they have little statistical significance.Conclusion:1. The expression of AQP1 is increased in diabetic nephropathy, and it is involved in the progression of diabetic nephropathy.2. The early damage of kidney in AQP1 knockout diabetes group is more serious than that in wild type diabetes group.3. Aquaporin-1 plays a protective role in diabetic nephropathy.