Expression Of COX-2 In Renal Interstitial Fibrosis And The Protective Effect Of Ginkgo Biloba Tablet

Renal interstitial fibrosi(sRIF)is the most important pathological procedure which exists almost all chronic nephropathy. Lots of research indicateed that the degree of renal interstitial fibrosis can prognosticate the level of renal function impairment and can determine the outcome of renal disease. The research of renal interstitial fibrosis is becoming the hot spot in international nephrology.It is still not unknown for the mechanisms of renal interstitial fibrosis because of its complex. Research indicated that it was important the renin-angiotensin system in the interstitial fibrosis, especially tissue local renin-angiotensin system. It has been known that one of the main mechanisms is local Ang II increasing in renal interstitial fibrosis. The effects of Ang II are not only it haemodynamic effect and promoting cell growth, but also regulating the cytokines net. Banding to the specific receptor in cell membrane is necessary for Ang II realize the effects above-mentioned. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) are the main angiotensin II receptors (ATR). ATIR plays the main role in realizing the biological effects of Ang II, well the effects of AT2R are not clearly. One of the main objects of this research is to investigate the inhibitory action of ginkgo leaf to AT1R.COX- 2 is a membrane binding protein which exits in the nuclear membrane and microsomal membrane. Research has been shown that COX-2 can express in human and many species animal kidney, including dogs, mice and macaque, but it is only low expression. It has been shown that COX-2 increasing in the kidney of elder and the patients of diabetic nephropathy, chronic cardiac insufficiency or hypertensive disease. One of the main objects of this research is to investigate the inhibitory action of ginkgo leaf to COX-2.The main methods applied in this research: Wistar rats were divided into four groups, which are sham group, UUO model group, benazapril group and ginkgo biloba tablet group (n=6). After ginkgo biloba tablet was given to UUO rats for 2 weeks, all rats were sacrificed, andα-SMA,Col-Ⅰ,AT1R and COX-2 expression were detected by immunohistochemistry,COX-2 mRNA expression was detected by RT-PCR.The main results were as follows:1 morphology results:Comparing with the pathological changes of UUO group rats, ginkgo biloba tablet and benazepril group rats present alleviated renal lesions, in which interstitial fibrosis is not obvious and there is no obvious change in renal tubular epithelial cell.2 serology results:After rats administered 2 weeks, NAG enzyme activity, urine creatinine, serum creatinine, urea nitrogen and 24 h total urinary protein of ginkgo biloba tablet group rats were lower than those of UUO group rats(P<0.05).3 immunohistochemistry results:(1) After rats treated 2 weeks, ColⅠandα-SMA expression in renal interstitium of UUO group rats were higher significantly than that of sham group rats (P<0.01). ColⅠandα-SMA expression in renal interstitium of ginkgo biloba tablet and benazepril group rats were lower than those of UUO group rats (P<0.05).(2) AT1R expression increased significantly in UUO group compared to sham group (P<0.01); and Compared to UUO group, AT1R expression decreased significantly in ginkgo biloba tablet group and bebazeprilat group (P<0.05).(3) Compared to sham group, COX-2 expression increased significantly in UUO group (P<0.01); and Compared to UUO group, COX-2 expression decreased significantly in ginkgo biloba tablet group and bebazeprilat group (P<0.05).4 Results of RT-PCRCompared to sham group, COX-2 mRNA expression increased significantly in UUO group (P<0.05); and COX-2 mRNA expression decreased significantly in ginkgo biloba tablet group and bebazeprilat group compared to UUO group (P<0.05).The main conclusion of this research:1. For UUO rats, Ginkgo leaf praeparatum can delay renal function deterioration and lessen renal interstitium fibrosis through inhibiting ECM accumulation in renal interstitium. Therefore, Ginkgo leaf praeparatum possess protection to renal function and structure of obstructive nephropathy.2. The increasing of AT1R expression in UUO rats'kidney shows that Ang II, as the initiating agent of renal interstitial fibrosis, play important roles by binding to AT1R.3. COX-2 play an important role in the development of renal interstitial fibrosis. Once the content and/or activity be inhibited, the process of renal lesion can be delayed in some degree.4. ginkgo biloba tablet treatment can avoid the renal interstitial fibrosis and protective the renal function and many mechanisms take part in this process: (1) Inhibits the over expression of AT1R, which decrease the binding capacity of Ang II to AT1R; (2) The expression of COX-2 were decreased directly or indirectly, and then the prostaglandin produce decreased.