Effect of selective cyclooxygenase -2 inhibitor on the renal lesion of streptozotocin-induced diabetic rats and its possible mechanism

Yiqin Zuo, Yong Gu, J. Ma, Shantan Lin

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3 Scopus citations

Abstract

OBJECTIVE: To investigate the effect of selective cyclooxygenase (COX)2 inhibitor-meloxicam on the renal lesion of diabetic rats and its possible mechanism. METHODS: Twenty-nine rats were randomly divided into four groups: normal control rats (n = 6), streptozotocin (STZ)-induced diabetic rats without treatment (n = 8), STZ-induced diabetic rats treated with indomethacin (2 mg x kg(-1) x d(-1)) (n = 6), and STZ-induced diabetic rats treated with meloxicam (2 mg x kg(-1) x d(-1)) (n = 9). Sixteen weeks later, the blood sugar, blood urea nitrogen (BUN), and blood creatinine were examined. Radioimmunoassay was used to examine the prostaglandin(2) (PGE(2)) and Thromboxane B(2) (TXB(2)) in the urine. The expression of transforming growth factor -beta1 (TGF-beta1) and TGF-beta receptor type II (TbetaR2) of the renal cortex were measured by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Immuno-precipitation analysis was carried out to examine the protein level of angiotensin II type 1 (AT1) receptor. Periodic acid-Schiff staining was used to examine the morphological changes by light microscopy. RESULTS: In the STZ-induced diabetic group, the blood levels of sugar, BUN, and creatinine were higher, and the creatinine clearance (Ccr) was remarkably higher in comparison with those in the normal control group (P < 0.05). Ccr was lower in diabetic rats treated with indomethacin and diabetic rats treated with meloxicam than in diabetic rats without treatment (P < 0.05). There was no difference of blood creatinie among these three groups. The blood sugar level in diabetic rats treated with meloxicam was lower than those in the diabetic rats treated with indomethacin and untreated group (all P < 0.05). The renal weight/body weight ratio was significantly higher in the untreated group than that in the control group. The PGE(2), TXB(2) and albumin levels in urine of STZ-induced diabetic rats were 1,641 +/- 288 pg/24 h 5,507 +/- 1,359 pg/24 h, and 46.3 +/- 9.5 microg/24 h respectively, much higher than those in meloxicam group (910 +/- 255 pg/24 h, 3,272 pg/24 h +/- 670 pg/24 h and 17.2 +/- 5.4 microg/24h respectively, all P < 0.01). The urine PGE(2) and albumin was 1,195 +/- 448 pg/24 h and 34.1 +/- 10.2 microg/24 h respectively in the indomethacin group. There was no difference in renal weight/body weight ratio and TXB(2) excretion between the untreated group and indomethacin group. The relative contents of TGF-beta1 and TbetaR2 mRNA expression in renal cortex of STZ-induced diabetic rats were 0.185 +/- 0.037 and 0.194 +/- 0.054, much higher than those in other groups. Glomerular hypertrophy, mesengial expansion, extracellular matrix accumulation, and sclerosis of partial glomeruli were seen in diabetic rats without treatment and those treated with indomethacin. The pathological changes were less in meloxicam group (P < 0.05). CONCLUSION: The selective COX-2 inhibitor meloxicam significantly suppresses TGF-beta1 and TbetaR2 genes expression, elevates the protein level of AT1 receptor and attenuate the renal lesion caused by diabetes. TGF-beta1 and AT1 receptor may be involved in the mechanism concerned.

Original languageEnglish (US)
Pages (from-to)239-243
Number of pages5
JournalZhonghua yi xue za zhi
Volume82
Issue number4
StatePublished - Feb 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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