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Background:Aldose Reductase (AR), one of oxidative stress sensitive enzymes, widely distributes in a form of a monomeric protein in kidney, AR can be activated by increased oxidative stress or inflammation or high expression of TGF-β. And it also involves in other pathological processes associated with proliferation of mechanocyte and mesangial cells, transition of tubular epithelial cells and deposition of extracellular matrix. Finally, it induces glomerulosclerosis and interstitial fibrosis which is the basic element leading to hypertensive renal injury. Also, our previous study has proved that there was obvious relationship between activated AR and hypertensive cardiac and vascular remodeling. And the remodeling was markedly improved in AR inhibitor group. The pre-test has already demonstrated that the activity and expression of AR in SHR rats could be lowered by Eucommia Lignans that could protect hypertensive myocardium. Therefore, we prospect that Eucommia Lignans might inhibit AR in kidney and improve hypertensive renal injury.Objective:To study the effect and mechaism of Eucommia Lignans on Aldose Reductase in kidney and hypertensive renal injury,Methods:There were two parts, in vivo and in vitro, in our experiment. In vivo, five groups are randomly divided into normal control group (WHY+ water, n=7), hypertensive group (SHR+water, n=7), Captopril treated hypertensive group (SHR+ACEI,100 mg·kg-1·d-1, n=7) as a positive group, Epalrestat treated hypertensive group (SHR+ARI,100 mg·kg-1·d-1, n=7) and Eucommia Lignans treated hypertensive group (SHR+Eucommia Lignans,300 mg·kg-1·d-1, n=7). The blood pressure was taken every four weeks. In the 25 weeks, we detected NAG activity in fresh urina sanguinis, ALB and UCR in 12 hours urine. Also, TEM images and Sirius red staining were used to detect morphological change in each group. And MTT in vitro demonstrated proliferation of mesangial cells. Immunohistochemistry and realtime PCR in vitro have shown differences in translative and transcriptive lever of AR expression.Results:(1) Mean arterial pressure in Captoril and Eucommia Lignans was lowered compared to SHR group, but there was no obvious change in Epalrestat group. (2) Eucommia Lignans and Epalrestat could lower NAG enzyme activity in SHR rats (P< 0.05). And compared to SHR rats, the value K stands for the ratio of ALB and UCR, was decreased markedly in the last three groups (P< 0.05). (3) The edge of basement membrane in WKY group seemed clear and in a uniform thickness. But in SHR group, there was obviously uneven thickness and extensive tearing. And improvement to some degree has been seen in Captoril group. The shape and structure in last two groups was much better than SHR group. (4) Morphological detection suggested that significant damage in SHR rats compared to normal pressure group. But in Epalrestat and Eucommia Lignans group Sirius red around microvasclular, of which OD in sequency was 0.028±0.010,0.056±0.007, 0.030±0.009,0.016±0.007和0.030±0.007. And number of mesangial cells, especially in 48 and 72 h, were much less than SHR group (P<0.05).(5) The protein in each group was 0.028±0.010、0.056±0.007、0.030±0.009、0.016 0.007和0.030±0.007 in turn. And mRNA lever in Eucommia Lignans group was lessen much without the dosage dependent compared to SHR rats group (P<0.05), and was more or less the same as WKY, Captoril and Epalrestat groups.Conclusion:(1)、There is an increasing expression of AR in SHR rats kidney. (2)、Both Eucommia Lignans and Captopril could inhibit Aldose Reductase in kidney of SHR rats. (3)、Both Eucommia Lignans could improve hypertensive renal injury by inhibiting expression of III collagen and proliferation of mesangial cells.
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