| [Background and Objective]"Inducible" cyclooxygenase-2(COX-2) has been becoming the hot research topic after being found since 1989. However, most of such researches focused on inflammation and tumor, and it was less in the aspect of renal. Documents showed that the expression of COX-2 in the normal renal tissue were mainly in the macula densa, in arterioles and veins and in medullary interstitial cells and it connected closely with hemodynamic changes, salt excretory and renal cell proliferation. In some renal animal models, not only constitutive COX-2 but also inducible COX-2 was demonstrated in the kidney. For example, in a rat model of 5/6 renal ablation, compared with the sham-operated group, COX-2 and immune globin have increased in the renal cortex of the operated group, but COX-1 with no differences. Thus, COX-2 plays an important role in renal cell proliferation that can be concluded. In unilateral ureteral obstuction(UUO) animal models, the blood volume of the operated group and glomerular filtration rate decreased greatly. COX-2 expression in renal cortical declined, but increased in medulla. Unlike COX-2, the levels of COX-1 is of no differences between renal cortex and medulla.Therefore,COX-2-induced prostaglandins may be contributed to the distribution of renal blood. In addition, COX-2 appears to be up-regulation in anti-glomerular basement membrane antibody glomerulonephritis, mesangioproliferative glomerulonephritis and passive Heymann nephritis. Thus, COX-2 may participate in the mechanism of some nephritis. So far,the investigationof COX-2 in patients with active lupus nephritis is not reported in China. Studies showed that interleukin-l(IL-l), interleukin-6(IL-6) and tumor necrosis factor(TNF) stimulated "Inducible"COX-2 expression in inflammatory cell. COX-2-derived prostaglandins(PGs)are involved in the inflammation and tissue damage. Recent investigation on lupus nephritis(LN) found that interleukin-1 and interleukin-6 increased evidently in the blood monocytes of LN patients. We do not know whether the inflammatory cells in LN could express COX-2 by the stimulation of some cytokine. In this research, we compared the renal tissue of LN with normal renal tissue, adopted immunohistochemistry to analyze the expression of COX-2 and the correlation between COX-2 and macrophage signed with CD68,and studied the clinical significance.[Methods] Renal tissue were assigned to two groups: the control group and thelupus nephritis (LN) group. The 25 renal tissue samples were made by renal biopsy from the lupus nephritis patients in Nephrology Department of the First Affiliated Hospital of Zhengzhou University, from March, 2004 to Oct, 2004, who diagnosed as systemic lupus erythematosus( SLE) according to the American College of Rheumatology revised criteria for classification of SLE in 1997 .These cases were divided into three subtype including 6 LN II, 7 LN Ilia and 12 LNlVa according to the classification standard of International Society Nephrology and Renal Pathology Society. The 6 cases normal renal tissue given by Urology. The 24-hour urinary protein excretion, complement C3, plasma creatinine and creatinine clear rate of the patients with LN had been tested before renal biopsy. The renal tissue samples were analyzed histologically, including HE and Masson staining, and immunohistochemically with the PV staining measured to COX-1, COX-2 and CD68.[Results](1) There were no differences in the expression of COX-1 in glomeruli between control group and LN group(24.35± 11.92 vs. 23.57±16.16 P>0.05) (24.20±11.36 vs. 23.57±16.16 P>0.05) (24.43±11.26 vs. 23.57±16.16 PX).O5), and the same with subtype of LN (24.20 +11.36 vs 24.35 ± 11.92 P>0.05) (24.43 + 11.26 vs.24.35 +11.92 P>0.05), (24.43 + 11.26 vs24.20 ± 11.36 P >0.05) . There were no differences in the expression of COX-1 in tubulointerstitium between control group and LN group (84.83±22.55 vs. 82.03±17.08 P>0.05)( 86.66±23.08 vs. 82.03±17.08 />>0.05) ( 86.88±19.58 vs. 82.03±17.08 P>0.05),similarly of that in subtype of LN (86.66+23.08 vs. 84.83 ±22.55 P>0.05) (86.88 + 19.58 vs. 84.83 ±22.55 P>0.05) (86.88 + 19.58 vs. 86.66+23.08 P>0.05)(2) Compared with control group, the expressions of COX-2 in glomeruli all increased significantly in LNII, LNIIIa, LNlVa group (17.77±8.02 vs.3.57±1.56 PO.01) (41.01±9.21 vs. 3.57±1.56 P<0.01) (69.88±10.44 vs. 3.57±1.56 PO.01), and the same with subtype of LN (41.01 +9.21 vs.17.77 + 8.02PO.01) (69.88 ±10.44 vs. 17.77 ± 8.02 PO.01) (69.88±10.44 vs. 41.01 ±9.21 PO.01) .Compared with control group, the expressions of COX-2 in tubulointerstitium all increased significantly in LN II, LNIIIa, LN IVa group (191.35±43.43 vs. 52.47±24.50 PO.01) (295.23±37.09 vs. 52.47±24.50 P<0.01) (375.67±53.27 vs. 52.47±24.50 i><0.01), similarly of that in subtype of LN (295.23±37.09 vs. 191.35+43.43 P<0.0\) (375.67 ±53.27vs. 191.35 + 43.43 P<0.0\) (375.67±53.27 vs. 295.23±37.09 P<0.01)(3) Compared with control group , the expressions of macrophage signed with CD68 in glomeruli increased obviously in LNII, LNIIIa, LNlVa group (5.49±1.58 vs. 0.90±0.52 i><0.01) (12.4±3.43 vs. 0.90±0.52 P<0.01) (18.65±.54 vs. 0.90±0.52 PO.01), and the same with subtype of LN (12.4± 3.43 vs.5.49± 1.58 /><0.01)( 18.65 ±.54 vs.5.49±1.58 PO.01X 18.65 + .54 vs. 12.4±3.43 .P<0.01) . Compared with control group , the expressions of macrophage signed with CD68 in tubulointerstitium increased obviously in LNII, LNIIIa, LNlVa group (136.77±40.32 vs. 36.78±19.31 PO.01) (233.4±47.19 vs. 36.78±19.31 P<0.01) (379.74±58.01 vs. 36.78±19.31 PO.01), similarly of that in subtype of LN (233.4±47.19 vs. 136.77+40.32PO.01) ( 379.74 ±58.01vs.l36.77± 40.32 P<0.01) ( 379.74 ±58.01vs. 233.4+47.19 P<0.01)(4) The positive correlation between the expressions of macrophage signed with CD68 and COX-2 in glomeruli and tubulointerstitium in LN group.(r=0.80 P<0.01)(r=0.82P<0.01)(5) The expression of COX-2 in glomeruli and tubulointerstitium in LN group show a strong positive correlation with lupus nephritis pathology activity(r=0.67 P<0.01 Xr=0.83 P<0.01),as well as proteinuria per day(r=0.65 P<0.01)(r=0.68 PO.01). No correlation with complement C3 are found. (r=-0.29 P>0.05) (r=-0.37 P>0.05).However, we examined the negative correlation with creatinine clear rate(r=-0.47 PO.01) (r=-0.59 P<0.01).[Conclusions](1) The expression of COX-2 and the macrophage in the renal tissue of patients with active lupus nephritis raised with the aggravation of pathological changes, and connected closely. These results suggested that COX-2 and the macrophage were involved in the inflammatory course in lupus nephritis.(2) The high expression of COX-2 in the renal tissue of patients with active lupus nephritis influenced lupus nephritis pathology activity and renal function. These results showed that COX-2 inhibitor might play a protective role in lupus nephritis. |
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