The Effect Of Rac1 Inhibitor To TGF-β1 And Type Ⅲ Collagen Expressions On Renal Damage In Salt-sensitive Hypertensive Rats

Objective:To observe the effect of Rac1 inhibitor to TGF-β1 and type III collagen expression on renal damage of salt-sensitive hypertensive rats and investigate the mechanisms of Rac1 on renal damage in salt-sensitive hypertension.Methods:A total of 30 male SD rats underwent left uninephrectomy, and only 22 rats survived and were randomly divided into three groups: control group(n = 6), model group and treated group. Control rats were subcutaneously injected by vegetable oil and drank tap water. The two other groups were subcutaneously injected by Desoxycorticosterone acetate(DOCA) at 30mg/(kg·week) and 1% saline for drinking until the end of this experiment.Twelve rats were qualified and randomly divided into model group(n = 6) and treated group(n = 6). At the beginning of 9th week, rats in treated group were subcutaneously injected by Rac1 inhibitor NSC23766 at 1mg/(kg·d), and the two other groups received the same amount of saline subcutaneous injection for the next 4 weeks. Blood pressure was monitored once per week. At the 0, 4, 8 and 12 weeks, 24-hour urinary protein was assayed,and at the end of this experiment, HE,Msson and PAS staining was done in right renal tissue specimens to evaluate renal tubular histology variation. The expression levels of TGF-β1, type III collagen and Rac1 in renal tissue were meadured.Results:Compared with the control group,4 week the average arterial pressure were increased,12 week the mean arterial pressure in the model group [(123.1±6.76)vs(84.3±5.08)] is more than the control group(both P < 0.05), Compared with the model group, the blood pressure in the treated group is lower than the control group significantly(P < 0.05).The 24-hour urine protein levels were significantly higher in model group than in control group and in treatment group(both P < 0.05).The expressions ofrenal TGF-β1, type III collagen and Rac1 were up-regulated in model group, and NSC23766 were observed to inhibit the upregulation of renal TGF-β1, type III collagen and Rac1 in treated group.The control group rats showed almost normal tubulointerstitium,howerve,Model group rats exhibited seriously tubulo-interstitial fibrosis.Treatment with NSC23766 significantly attenuated Rac1 induced renal injuries mentioned above.Conclusions:Rac1 might play an important role in renal injure process in the salt-sensitive hypertensive rats, which might be mediated through the TGF-β1 and the resultant type III collagen deposition.