尼美舒利对吲哚美辛诱导的大鼠胃黏膜损伤的保护作用

目的探讨尼美舒利对胃黏膜的保护作用及其可能的作用机制。方法大鼠禁食12h后,ig给予吲哚美辛30mg·kg-1制备急性胃黏膜损伤模型,5min后分为模型对照、尼美舒利100mg·kg-1、塞来昔布100mg·kg-1、美洛昔康4mg·kg-1、双氯芬酸钠50mg·kg-1和布洛芬600mg·kg-1组,分别ig给予相应药物;另设正常对照组。6h后处死所有大鼠,测定胃溃疡面积。生化比色法检测大鼠胃组织和血清中谷胱甘肽(GSH)和丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果正常对照组大鼠胃黏膜表面光滑,黏膜皱襞纹理清晰;模型组大鼠均见急性胃溃疡,溃疡面积为(10.6±7.4)mm2;与模型组比较,尼美舒利和塞来昔布组胃溃疡面积显著减小,分别为4.1±1.7和(4.9±3.2)mm2(P<0.01);美洛昔康组未见明显变化,为(8.1±3.5)mm2;双氯芬酸钠和布洛芬组胃溃疡面积明显增加,分别为15.4±4.8和(16.0±7.3)mm2(P<0.01)。与正常对照组比较,模型组大鼠胃组织中GSH含量和SOD活性明显降低(P<0.05),MDA含量显著升高(P<0.01);血清中MDA含量显著升高(P<0.01),而GSH含量和SOD活性变化不明显。与模型组相比,尼美舒利组胃组织中GSH含量和SOD活性明显升高(P<0.05,P<0.01),MDA含量明显降低(P<0.01);血清中GSH含量明显增加(P<0.01),MDA含量明显降低(P<0.01);塞来昔布组大鼠胃组织中SOD活性明显升高(P<0.01),血清中MDA含量明显降低(P<0.01),其他指标无明显变化;美洛昔康、双氯芬酸钠和布洛芬对模型大鼠胃组织和血清中GSH,MDA含量及SOD活性均无明显影响。结论尼美舒利对吲哚美辛诱导的大鼠急性胃黏膜损伤具有明显的保护作用,作用机制可能与其抗氧化活性有关。     

Aspirin and COX-2 inhibitor nimesulide potentiate adrenergic contractions of human gastroepiploic artery

BACKGROUND: The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine. METHODS: Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition. RESULTS: The COX-1 and COX-2 inhibitor aspirin at high concentrations (10(-6) to 10(-5) mol/L) and the COX-2 inhibitor nimesulide (10(-6) mol/L) potentiated the contractile responses of the arterial rings to sympathetic neurogenic stimulation and norepinephrine. In contrast, lower concentrations of aspirin (10(-8) to 10(-7) mol/L) or the COX-1 inhibitor SC-560 (3 x10(-8) mol/L) did not affect these responses. The vascular relaxation induced by acetylcholine was not affected by COX-1 and COX-2 inhibition. CONCLUSIONS: The results provide functional evidence that vasodilator prostaglandins are active components of the response of human gastroepiploic artery to neurogenic stimulation and norepinephrine. Aspirin at high concentrations and the COX-2 selective inhibitor nimesulide potentiated the contractile response of gastroepiploic artery to adrenergic stimulation by inhibiting COX-2-derived PGI(2). Aspirin at low concentrations and the COX-1 selective inhibitor SC-560 did not modify the contractile responses, possibly due to minor importance of vasoconstrictor prostaglandins (TXA(2)) as active components of the response of gastroepiploic artery to adrenergic stimulation.     

Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats

Context: Doxorubicin (DX) is a highly effective chemotherapeutic agent used widely in the treatment of solid tumors; however, its optimal use was associated with cardiotoxicity and nephrotoxicity. The exact mechanism of DX-induced cardiotoxicity and nephrotoxicity is not fully explored. Induction of cyclooxygenase-2 (COX-2) activity in either cardiac or renal tissue by DX has been previously reported, indicating a possible role of COX-2 in DX-induced tissue injury. However, the nature of this role in either tissue injury is an issue of controversy.

Objective: This study was the first that simultaneously evaluated the effects of a selective COX-2 inhibitor, nimesulide, and a non-selective COX-inhibitor, indomethacin, on DX-induced cardiotoxicity and nephrotoxicity in male Wistar rats.

Materials and methods: Rats were allocated into four groups. Control group, DX group (received 15 mg/kg, ip), DX + nimesulide (10 mg/kg/day, po) group, and DX + indomethacin (2 mg/kg/day, po) group. Nimesulide and indomethacin were started at the same day of DX injection and continued for 5 days.

Results: The results of the present study showed that inhibition of COX-2 either by selective or non-selective COX-2 inhibitor ameliorated DX-induced cardiotoxicity but aggravated DX-induced nephrotoxicity in rats, as evidenced biochemically and histopathologically.

Discussion and conclusion: Our study indicates that production of COX-2 is organ specific; consequently, the differential effect of COX-inhibitors should be considered in DX-treated patients. However, a wide scale experiment is needed for further confirmation and testing other members of COX-inhibitors (e.g. celecoxib and diclofenac).     

HPLC测定尼美舒利含量

 目的：用高效液相色谱法测定尼美舒利的含量。方法：以ODS-C₁₈反相柱、水（1g/LNa₂HP0₄溶液)-甲醉(30：70)为流动相，以二苯甲酮作内标，检测波长254 nm。结果：尼美舒利在10?60/xg/ml的浓度范围内，线性关系良好。回归方程:Y=0.0094+0.0203X,r=0.9998。结论：方法精密，专一，灵敏，且在此条件下，可将尼美舒利与其 含有的杂质较好地分离。     

Electrochemical Generation and Interaction Study of the Nitro Radical Anion from Nimesulide

Pharmaceutical Research -     

尼美舒利治疗类风湿关节炎和骨性关节炎的临床研究

目的：观察国产尼美舒利对类风湿关节炎（ＲＡ）和骨性关节炎（ＯＡ）的疗效和安全性。方法：选取ＲＡ患者５９ 例和ＯＡ患者４４ 例。ｐｏ 尼美舒利片１００ ｍｇ,ｂｉｄ;对照组ｐｏ 布洛芬缓释胶囊３００ｍｇ,ｂｉｄ。治疗时间为４ｗｋ。分别观察治疗前后临床指标和炎性实验指标的变化。结果：尼美舒利治疗ＲＡ４ｗｋ 后,疼痛程度、压痛关节数、关节压痛指数、关节肿胀指数、握力、晨僵时间、血沉均显著改善。对ＲＡ的总有效率为８３．３％ 。治疗ＯＡ４ｗｋ 后,膝关节活动痛、１５ｍ 行走时间、日常活动能力及病人综合评估均有显著改善。对ＯＡ的总有效率为７５．０％ 。其不良反应总发生率为１９．２％ , 以胃肠道反应为常见（９．６％）。尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率与布洛芬相比均无显著性差异。结论：尼美舒利对ＲＡ和ＯＡ的疗效及不良反应的发生率均与布洛芬相当。     

Effects of a COX-2 Preferential Agent Nimesulide on TNBS-Induced Acute Inflammation in the Gut

In inflammatory bowel disease, increased production of prostaglandins by cyclooxy- genase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE₂ metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation. None of the studied drugs reduced the size of inflammatory mucosal lesions in the colon. In TNBS-induced acute inflammation of the colon, nimesulide reduced the formation of inflammatory edema, probably by a mechanism related to inhibition of PGE₂ production by COX-2 pathway. In addition, nimesulide inhibited neutrophil infiltration into inflamed mucosa mimicking the action of dexamethasone.     

高效液相色谱法测定家兔血浆中尼美舒利的含量

目的 建立HPLC测定尼美舒利(nimesulide，NM)血药浓度的方法。方法 以Shim-pack Vp-ODS为分离柱，流动相：甲醇-水-冰醋酸(60：40：1)，内标：地西泮，检测波长230nm。结果 NIM的血药浓度在1-100μg/mL范围内与峰面积呈良好线性关系，日内精密度、日间精密度均小于10％，平均回收率分别为105.8，97．55，96．89％。结论 本法可用于测定血血浆中尼美舒利的含量。