摘要
目的 探讨选择性环加氧酶 2抑制剂莫比可对糖尿病大鼠肾脏病变的影响。方法 将大鼠分成正常对照组 (6只 )、不用药组 (8只 )、消炎痛组 (6只 )和莫比可组 (9只 )。 16周后放射免疫法测定大鼠尿液中前列腺素E2 (PGE2 )和血栓烷素B2 (TXB2 )的排泄量 ,应用逆转录 聚合酶链式反应和免疫沉淀的方法分别检测肾皮质中转化生长因子 β1(TGF β1)及其Ⅱ型受体 (TβR2 )的基因表达和血管紧张素Ⅱ 1型受体 (AT1R)的蛋白水平 ,并观察PAS染色下肾脏的病变情况。结果 与正常对照组相比 ,糖尿病大鼠PGE2 和TXB2 排泄增多 (分别为 16 4 1pg/ 2 4h± 2 88pg/ 2 4h ,5 5 0 7pg/ 2 4h± 135 9pg/ 2 4h)。TGF β1和TβR2 的基因表达显著上调 ,分别为 0 185± 0 0 37,0 194± 0 0 5 4。AT1R的蛋白水平下降 2 1 3%。光镜显示肾小球系膜区增宽 ,PAS染色阳性的胶原沉积增多。消炎痛、莫比可均能不同程度地减少PGE2 的生成 (P <0 0 5 ) ,但TXB2 仅在莫比可组显著下降。莫比可组TGF β1和TβR2 基因表达明显下调 (39% ,4 7% ) ,AT1R的蛋白水平回升 (P <0 0 5 ) ,肾脏病变有所好转 ,而消炎痛无效。结论 莫比可对糖尿病肾脏病变具有一定的保护作用 ,其机制可能与调节TGF
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·kg -1 ·d -1 ) ( n =6), and STZ induced diabetic rats treated with meloxicam (2mg·kg -1 ·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 β1 (TGF β1) and TGF beta receptor type II (TβR2) 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 signicantly 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 μg/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 μg/24h respectively, all P <0 01). The urine PGE 2 and albumin was 1 195±448 pg/24 h and 34 1±10 2 μg/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 β1 and TβR2 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 suppressess TGF β1 and TβR2 genes expression, elevates the protein level of AT1 receptor and attenuate the renal lesion caused by diabetes. TGF β1 and AT1 receptor may be involved in the mechanism concerned.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2002年第4期239-243,共5页
National Medical Journal of China
基金
教育部博士点基金资助项目
上海市曙光计划资助项目
