Anti-inflammatory,analgesic and antioxidant activities of 3,4-oxo-isopropylidene-shikimic acid

Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid (SA). SA is extracted from the dry fruit of Illicium verum Hook. f. (Magnoliaceae), which has been used for treating stomachaches, skin inflammation and rheumatic pain.

Objective To investigate the anti-inflammatory, analgesic and antioxidant activities of ISA.

Materials and methods Analgesic and anti-inflammatory activities of ISA were evaluated using writhing, hot plate, xylene-induced ear oedema, carrageenan-induced paw oedema and cotton pellets-induced granuloma test, meanwhile the prostaglandin E₂ (PGE₂) and malondialdehyde (MDA) levels were assessed in the oedema paw tissue. ISA (60, 120 and 240?mg/kg in mice model and 50, 120 and 200?mg/kg in rat model) was administered orally, 30?min before induction of inflammation/pain. Additionally, ISA was administered for 12 d in rats from the day of cotton pellet implantation. The active oxygen species scavenging potencies of ISA (10^?3–10^?5 M) were evaluated by the electron spin resonance spin-trapping technique.

Results ISA caused a reduction of inflammation induced by xylene (18.1–31.4%), carrageenan (7.8–51.0%) and cotton pellets (11.4–24.0%). Furthermore, ISA decreased the production of PGE₂ and MDA in the rat paw tissue by 1.0–15.6% and 6.3–27.6%, respectively. ISA also reduced pain induced by acetic acid (15.6–48.9%) and hot plate (10.5–28.5%). Finally, ISA exhibited moderate antioxidant activity by scavenging the superoxide radical and hydroxyl radical with IC₅₀ values of 0.214 and 0.450?μg/mL, respectively.

Discussion and conclusion Our findings confirmed the anti-inflammatory, analgesic and antioxidant activities of ISA.     

Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats

Abstract

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.     

3，4-O-异亚丙基莽草酸（ISA）在Beagle犬体内的药代动力学研究

目的:建立 Beagle 犬血浆中3,4-O-异亚丙基莽草酸(ISA)的 RP-HPLC 分析方法,并对 ISA 原料药静注给药在犬体内药动学过程进行分析研究。方法:犬血浆样品中加入内标物芦丁,采用酸性甲醇沉淀蛋白质并提取药物,采用 RP-HPLC法测定。大连依利特 Hypersil ODS 2柱(250 mm×4.6 mm,5μm);流动相:甲醇-0.3%醋酸(50:65);检测波长:220 nm;柱温:室温;流速:1.0 mL·min~(-1)。动物实验使用 Beagle 犬6只,采用静脉注射给药(200 mg·kg~(-1)),进行血药浓度测定。结果:犬血浆样品中 ISA 无干扰,以芦丁为内标,测定血药浓度最低检测限3 ng·mL~(-1);ISA 浓度在0.01～600μg·mL~(-1)范围内对ISA 峰面积和内标峰面积的比有较好的线性关系,r=0.9996,绝对回收率大于70%,方法回收率在98.5%～103.3%之间;日内精密度、日间精密度 RSD 分别小于5%和15%。ISA 原料药静脉注射在犬体内过程符合二室模型。结论:本法准确、灵敏度较高,可用于 ISA 体内过程的研究。     

Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study examined the effect of NF-kappaB inhibitor and antioxidant, pyrrolidinedithiocarbamate (PDTC) on experimental ulcerative colitis in rats. Animals were randomly divided into 4 groups, each consisting of 6 animals; normal control group, acetic acid group, PDTC-treated group and sulfasalazine-treated group as a positive control group. Induction of colitis by intracolonic administration of 3% acetic acid produced severe macroscopic inflammation in the colon 24 h after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, oedema and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), and nitrite/nitrate and colonic concentrations of tumor necrosis factor-alpha (TNF-alpha) and the neutrophil infiltration index, myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxides formation and depleted reduced glutathione concentrations (GSH) in colonic tissues. Immunohistochemical studies of colonic sections revealed upregulation of inducible nitric oxide synthase (iNOS). Pretreatment with PDTC at a dose of (200 mg/kg/day, i.p.), three days before induction of colitis decreased serum LDH, nitrite/nitrate and TNF-alpha levels, colonic concentrations of MPO and lipid peroxides while increased colonic GSH concentration. Moreover, PDTC pretreatment attenuated colonic iNOS expression. Finally, histopathological changes were nearly restored by PDTC pretreatment. The findings of the present study provide evidence that PDTC may be beneficial in patients with inflammatory bowel disease.     

异亚丙基莽草酸对H2O2损伤血管内皮细胞的保护作用

目的研究异亚丙基莽草酸(ISA)对血管内皮细胞损伤的保护作用。方法倒置显微镜下观察细胞形态学改变,MTT比色法检测细胞活性,用硝酸还原酶法测定细胞培养液中NO的含量。放射免疫法测定细胞培养液中前列环素代谢物6-酮-前列腺素F_1α(6-keto-PGF_1α)含量,比色法测定培养液及细胞裂解液的乳酸脱氢酶(LDH)活性并计算LDH的释放率。结果ISA可明显改善H₂O₂所致的内皮细胞变形、皱缩等损伤表现。1～100 μmol·L^-1 ISA可浓度依赖性的减轻H₂O₂引起的细胞活性降低和LDH释放,并促进H₂O₂诱导的血管内皮细胞释放NO和前列环素。结论异亚丙基莽草酸对H₂O₂损伤血管内皮细胞具有保护作用。     

苯烯莫德对实验性银屑病的治疗作用

目的观察苯烯莫德对实验性银屑病的影响。方法体外培养永生化人角质生成细胞Ha Ca T,用MTT法测试苯烯莫德的抑制率,免疫组化法观察角蛋白19(CK19)的表达。体内试验以维A酸乳膏为阳性对照,观察0.5%、1%、2%苯烯莫德药效(苯烯莫德低、中、高剂量组),并设阴性对照组。雌性性成熟小鼠60只,雌二醇诱导小鼠动情期阴道上皮有丝分裂模型成功后随机分组,从阴道注入样品(50μL),检测阴道组织有丝分裂指数。60只小鼠随机分组,给药前各组动物均用尼龙刷轻刷尾根0.5 cm处100次制作小鼠尾部颗粒层鳞片数模型,然后在同一部位涂抹给药(100μL),计数给药部位每100个鳞片中有颗粒层的鳞片数。80只豚鼠随机分组,普萘洛尔诱导豚鼠耳背部银屑病样模型成功后涂抹药剂(约200μL)于豚鼠耳背,取给药部位皮肤显微测表皮厚度。结果体外试验显示苯烯莫德对Ha Ca T细胞的IC50为28.5μg·m L-1,Ha Ca T细胞在20μg·m L-1苯烯莫德中培养,有大量CK19生成。苯烯莫德能抑制小鼠阴道上皮细胞的有丝分裂,苯烯莫德各剂量组有丝分裂细胞指数低于赋形剂组(P<0.05或P<0.01),苯烯莫德中、高剂量组低于苯烯莫德低剂量组(P<0.05,P<0.01)。苯烯莫德处理后能增加含颗粒层的鳞片数,苯烯莫德各剂量组小鼠尾部有颗粒层的鳞片比率高于赋形剂组(P<0.05或P<0.01),苯烯莫德中、高剂量组高于苯烯莫德低剂量组(P<0.05,P<0.01)。普萘洛尔诱导的豚鼠耳背部表皮的厚度增加能够被苯烯莫德抑制,苯烯莫德各剂量组表皮厚度薄于赋形剂组(P<0.05或P<0.01),苯烯莫德高剂量组薄于苯烯莫德低剂量组(P<0.05)。结论苯烯莫德具有明显治疗实验性银屑病的作用,具有开发前景。     

丹酚酸B对糖尿病大鼠肾纤维化的改善作用及其机制

目的观察丹酚酸B对糖尿病大鼠肾纤维化的影响,并探讨其可能机制。方法采用高糖高脂饮食,合并腹腔注射链脲佐菌素(STZ)的方法建立糖尿病大鼠模型。将糖尿病大鼠随机分为模型组、丹酚酸B低、高剂量组(80、160 mg·kg~(-1))。丹酚酸B各组每天灌胃给予相应剂量药物,正常对照组和模型组灌胃相应容量生理盐水,连续6周。实验结束时检测大鼠空腹血糖(FBG)、血清肌酐(SCr)、尿素氮(BUN)、尿微量白蛋白(UAlb),以及血清丙二醛(MDA)、总抗氧化能力(TAC)和超氧化物歧化酶(SOD)水平;Masson染色法观察肾组织胶原纤维水平;ELISA法检测肾组织Ⅰ型和Ⅲ型胶原含量;Western blot法检测肾组织转化生长因子β1(TGF-β1)、p-Smad2和Smad7蛋白水平。结果丹酚酸B可明显减少糖尿病大鼠肾组织胶原沉积,降低FBG、BUN、UAlb、SCr、MDA及TGF-β1、p-Smad2蛋白水平,使血清TAC、SOD活性和肾组织Smad7蛋白水平明显升高(P<0.01或P<0. 05)。结论丹酚酸B可明显减轻糖尿病大鼠肾纤维化,改善肾功能,其机制与改善氧化应激状态、调控TGF-β1/Smad信号通路有关。     

3,4-oxo-isopropylidene-shikimic acid inhibits adhesion of polymorphonuclear leukocyte to TNF-α-induced endothelial cells in vitro

AIM：To examine the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) on human polymorphonuclear leukocyte (PMN) adhesion to human umbilical vein endothelial cells (HUVEC) and explore its mechanism. METHODS:Adhesion of PMN to HUVEC was measured by rose bengal staining assay. Cell-EL1SA and RT-PCR methods were used to examine the expression of adhesion molecules ICAM-1. Cell viability was detected with MTT assay.RESULTS: ISA (1-100μmol/L) effectively reduced PMN adhesion to TNF-α-induced HUVEC with the inhibitory rate from 17.2% to 53.5%, and exerted no effect on PMN adhesion to normal HUVEC. Adhesion molecule ICAM-1 surface protein and mRNA expression induced by TNF-α (400kU/L) were significantly inhibited by ISA. In addition, the cell viability of HUVEC was unchanged 48h after treatment with ISA. CONCLUSION: ISA inhibited TNF-α-stimulated PMN-HUVEC adhesion and expression of ICAM-1.     

甘草酸对幼鼠实验性结肠炎的治疗作用及其机制研究

目的探究甘草酸对幼鼠实验性结肠炎的治疗作用及其作用机制。方法将75只SD大鼠幼鼠随机分为对照组、模型组、柳氮磺胺吡啶组(0.5 g/kg)和甘草酸40、160 mg/kg组,每组各15只,制备实验性结肠炎模型的同时分别灌肠给药,连续7 d。观察大鼠一般情况,HE染色法观察大鼠结肠组织病理学变化并进行疾病活动指数(DAI)评分、黏膜损伤指数(CMDI)评定,酶联免疫法测定血清中白介素-4(IL-4)、白介素-17(IL-17)、白介素-1β(IL-1β)水平,逆转录-聚合酶链反应(RT-PCR)、Western blotting法检测大鼠结肠组织中NLRP3、白介素-1β(IL-1β)、凋亡相关斑点样蛋白(ASC)、半胱天冬酶(caspase-1)表达。结果与模型组比较,甘草酸组幼鼠体质量逐渐增加,症状改善;炎症细胞浸润有所减少,腺体破坏程度降低;DAI评分、CMDI评分均降低,呈剂量相关性(P0.05);IL-4水平升高,IL-17、IL-1β水平降低,呈剂量相关性(P0.05);NLRP3、ASC、caspase-1、IL-1βmRNA表达和蛋白表达均降低,呈剂量相关性(P0.05)。结论甘草酸能够治疗大鼠实验性结肠炎,可能与抑制NLRP3通路蛋白表达、降低炎症因子水平有关。     

Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats

Objectives Glycyrrhizin is the main water‐soluble constituent of the root of liquorice (Glycyrrhiza glabra). The study investigates the effect of glycyrrhizin on streptozotocin (STZ)‐induced diabetic changes and associated oxidative stress, including haemoglobin‐induced free iron‐mediated oxidative reactions. Methods Male Wistar rats were grouped as normal control, STZ‐induced diabetic control, normal treated with glycyrrhizin, diabetic treated with glycyrrhizin and diabetic treated with a standard anti‐hyperglycaemic drug, glibenclamide. Different parameters were studied in blood and tissue samples of the rats. Key findings Glycyrrhizin treatment improved significantly the diabetogenic effects of STZ, namely enhanced blood glucose level, glucose intolerant behaviour, decreased serum insulin level including pancreatic islet cell numbers, increased glycohaemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced diabetes‐induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, namely, serum superoxide dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal values after glycyrrhizin administration. Free iron in haemoglobin, iron‐mediated free radical reactions and carbonyl formation in haemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects of glycyrrhizin and glibenclamide treatments appeared comparable. Conclusion Glycyrrhizin is quite effective against hyperglycaemia, hyperlipidaemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment.     

The effects of selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimental colitis induced by acetic acid in rats

Several mediators may be involved in the pathogenesis of inflammatory bowel disease, as well as in experimental colitis. The present work was conducted to investigate the effects of the two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimentally induced colitis in rats. Rectal instillation of acetic acid was used to induce the colitis. Acetic acid treatment caused haemorrhagic diarrhoea and weight loss in rats. Celecoxib (5 mg/kg) or rofecoxib (2.5 mg/kg), when given twice daily by the oral route, reduced the degree of haemorrhagic diarrhoea and the weight loss produced. In addition, they produced a significant reduction in the degree of colonic injury, the rise in myeloperoxidase (MPO) levels, total nitric oxide synthetase (NOS) activity, platelet-activating factor (PAF), histamine levels and prostaglandin E2 levels. In contrast, there was a significant increase in the levels of reduced glutathione (GSH). Thus, the findings of the present study provide evidence that selective cyclooxygenase-2 inhibitors may be beneficial in patients with inflammatory bowel disease.     

Involvement of central opioid receptors in protective effects of methadone on experimental colitis in rats

Purpose

There are several lines of evidence on the protective roles of opioids in gastrointestinal inflammatory conditions. This study aims to distinguish the central and peripheral roles of methadone, a non-selective opioid receptor agonist, in an acute model of ulcerative colitis in male rats.

Methods

Ulcerative colitis was induced by intrarectal administration of acetic acid 4%. Methadone was injected subcutaneously (s.c.), 5 and 10 mg/kg, and intracerebroventricular (i.c.v.), 50 and 300 ng/rat. Opioid antagonists were employed. Methylnaltrexone (MNTX; 5 mg/kg, i.p.), a peripherally acting opioid receptor antagonist, and naltrexone (NTX; 5 mg/kg, i.p. and 10 ng/rat, i.c.v.), a peripherally and centrally acting opioid receptor antagonist were injected before methadone (10 mg/kg, s.c. and or 300 ng/rat, i.c.v.) administration. NTX (5 mg/kg, i.p. and 10 ng/rat, i.c.v.) were administered 30 min prior to administration of methadone (10 mg/kg, s.c. and 300 ng/rat, i.c.v.), respectively. MNTX (5 mg/kg, i.p.) was injected 30 min prior to methadone (10 mg/kg, s.c.). Seventy-two hours following colitis induction, macroscopic and microscopic mucosal lesions, and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined.

Results

Methadone (300 ng/rat, i.c.v.) and Methadone (5 and 10 mg/kg, s.c.) improved the macroscopic and microscopic scores through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally injected NTX significantly reversed methadone 10 mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300 ng/rat) showed the anti-inflammatory effect which was reversed by central administration of NTX (10 ng/rat).

Conclusions

The opioid receptors mainly the central opioid receptors may mediate the protective actions of methadone on the experimental model of inflammatory bowel disease in rat.

     

南极磷虾肽对去卵巢大鼠骨质疏松症的改善作用

目的：观察南极磷虾肽(peptides from Antarctic krill, AKP)对去卵巢大鼠骨代谢、骨密度(BMD)及骨生物力学的影响,探讨其对骨质疏松症的改善作用。方法：32只雌性Wistar大鼠随机分为4组：假手术组、模型对照组、阳性对照组(阿伦磷酸钠1mg/(kg.d))和南极磷虾肽组(1000mg/(kg.d)),大鼠摘除双侧卵巢后4周开始持续灌胃90d,分别检测血清雌二醇(E2)、血清骨代谢指标(骨源性碱性磷酸酶(BALP)、骨钙素(OCN)、I型前胶原羧基端前肽(PICP)、组织蛋白酶K(Cath-K)、I型胶原羧基端交联肽(CTX-I))和尿液中骨代谢指标(钙(Ca)、磷(P)、脱氧吡啶啉(DPD))含量,并测定大鼠骨密度和骨生物力学指标。结果：南极磷虾肽能显著改善去卵巢大鼠血清中BALP、OCN和PICP的分泌(P<0.01),降低血清Cath-K、CTX-I和尿Ca、P、DPD水平(P<0.01),改善去卵巢大鼠骨代谢的高转换率;南极磷虾肽能显著增加去卵巢大鼠BMD(P <0.01),改善其骨生物力学性能(P <0.01)。结论：南极磷虾肽具有改善去卵巢大鼠骨质疏松症的作用。     

MT对大鼠乙酸性结肠炎的影响及有关机制初探

目的　探讨褪黑素对大鼠乙酸性结肠炎的影响及有关机制。方法　制备大鼠乙酸性结肠炎模型 ,实验设正常对照组、模型对照组、阳性药物对照组 (5 氨基水杨酸 ,10 0mg·kg-1)、MT给药组 (2 5 ,5 0 ,10 0mg·kg-1) ,采用灌肠方式给药 ,每天 1次 ,给药时间从制备模型 2 4h后开始至实验结束共 7d ,正常及模型对照组均给予生理盐水灌肠。实验结束后观察大鼠结肠粘膜损伤指数 (CMDI)、粪便隐血实验(OB)、髓过氧化物酶 (MPO)含量和粘膜病理组织学 (HS)情况 ,并检测结肠组织丙二醛 (MDA)、谷胱甘肽过氧化物酶(GSH Px)、过氧化氢酶 (CAT)、超氧化物歧化酶 (SOD)、一氧化氮 (NO)含量。结果　乙酸性结肠炎大鼠结肠CMDI、HS、OB程度和MPO水平均比正常组明显升高 ,MT灌肠可减轻乙酸性结肠炎大鼠的CMDI和粪便OB程度 ,降低MPO水平 ,10 0mg·kg-1MT可改善结肠粘膜病理损伤。同时可见模型组大鼠结肠组织MDA、NO含量增加 ,SOD、GSH Px和CAT水平降低。MT可明显降低MDA、NO含量 ,增加GSH Px、SOD和CAT水平。结论　MT对乙酸性结肠炎大鼠结肠粘膜损伤具有保护作用     

Thymoquinone protects against experimental colitis in rats

The present work was done to investigate the possible effects of thymoquinone on acetic acid-induced colitis in rats. Colitis was induced by intracolonic injection of 3% acetic acid. Several parameters including macroscopic score, histopathological and biochemical, were determined to assess the degree of protection. Biochemical parameters such as myeloperoxidase activity, reduced glutathione levels, platelet activating factor (PAF) and histamine were measured following standard assay procedures. The study showed that pretreatment of rats for 3 days with thymoquinone (10 mg/kg) was able to give complete protection against acetic acid-induced colitis an effect significantly higher than sulfasalazine (500 mg/kg) control group. The smaller dose of thymoquinone (5 mg/kg) produced partial protection. Moreover, the biochemical and histopathological changes were reversed and brought towards the control. These results suggest a beneficial effect of thymoquinone against experimentally-induced colitis and the possible mechanism of the protective effects may be partly due to an antioxidant action.     

异亚丙基莽草酸对大脑中动脉栓塞大鼠脑组织自由基代谢的影响

目的　研究异亚丙基莽草酸 (ISA)对大脑中动脉栓塞模型 (MCAT)大鼠脑组织自由基代谢的影响。方法　采用三氯化铁致大脑中动脉栓塞模型 ,观察ISA对脑组织总超氧化物歧化酶 (T SOD)、Cu Zn SOD、谷胱甘肽过氧化物酶(GSH px)活力及丙二醛 (MDA)含量的影响。 结果　ISA2 0 0 ,10 0mg·kg-1可提高模型大鼠脑组织T SOD活力 ;ISA2 0 0 ,10 0 ,5 0mg·kg-1均可明显增加模型大鼠脑组织Cu Zn SOD和GSH px活力 ;ISA 2 0 0 ,10 0 ,5 0mg·kg-1对模型大鼠脑组织MDA升高有明显的抑制作用。结论　ISA可能通过减轻脑组织自由基损伤保护脑组织缺血性损伤     

别嘌醇缓释胶囊对高尿酸血症大鼠胃肠和皮肤的保护作用及机制

目的:考察长期(3个月)应用别嘌醇缓释胶囊对高尿酸血症大鼠胃、肠和皮肤的影响及机制。方法:60只雄性Wistar大鼠随机分为正常对照(NC)组,模型(M)组,别嘌醇缓释胶囊低(CL)、高剂量(CH)组,别嘌醇片低(TL)、高剂量(TH)组,每组10只。除NC组,其余各组采用腺嘌呤(100mg·kg-1·d-1)和乙胺丁醇(250mg·kg-1·d-1)连续灌胃3周后改为隔日1次,共12周造成大鼠高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释胶囊或别嘌醇片,在实验第12周末,测量各组大鼠的体质量、血尿酸和血清白细胞介素(IL)-1β含量,胃、肠和皮肤的病理改变,及皮肤中肿瘤坏死因子(TNF)-α表达情况。结果:CH组可降低高尿酸血症大鼠血尿酸水平,缓解大鼠的体质量降低(P0.01);与M和TL组,特别是TH组比较,CL和CH组可缓解大鼠胃、肠黏膜损伤;与M和TL组比较,CL和CH组降低大鼠血清IL-1β水平作用显著(P0.05);CL和CH组皮肤组织中TNF-α表达明显降低。结论:与别嘌醇片比较,长期应用别嘌醇缓释胶囊在降低血尿酸的同时表现出更好的胃、肠黏膜和皮肤保护作用;抑制TNF-α及IL-1β介导的炎症反应。     

The effect of Oren-gedoku-to on experimental colitis in rats.

In Japan and China, Oren-gedoku-to (a complex mixture of ingredients derived from plants) has been used as a herbal medicine in the treatment of inflammatory and ulcerative diseases. In other countries salicylazosulfapyridine has been used to treat inflammatory bowel disease. In this study, we have compared the effect of Oren-gedoku-to with salicylazosulfapyridine on trinitrobenzene-sulphonic acid-induced colonic damage in rats, a model representative of ulcerative colitis and Crohn's disease in man. Oren-gedoku-to was administered orally for one or two weeks over a range of doses. Tissue damage scores, body weight, spleen weight, colon wet weight and colon wall thickness were measured, and colonic tissue levels of interleukin-8 (IL-8), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and myeloperoxidase activity were examined. The results indicated that Oren-gedoku-to was effective in the treatment of inflammatory bowel disease in the rat model. Histological observation showed a quicker healing process of the lesions, and a reduction of inflammatory cell infiltration following administration of Oren-gedoku-to. The precise mechanism of action for Oren-gedoku-to is still unclear; however, the reduction of IL-8, LTB4, and PGE2 observed suggests that the mechanism may be different from salicylazosulfapyridine (which has no effect on IL-8). There may be a potential benefit in offering combination therapy for the treatment of inflammatory bowel disease.     

实验性溃疡性结肠炎大鼠模型的建立

目的采用三硝基苯磺酸（TNBS）诱导大鼠溃疡性结肠炎动物模型,探讨与人溃疡性结肠炎（UC）的相似程度。方法 TNBS/乙醇法制作溃疡性结肠炎动物模型,分别于造模后1、3、7周3个时间段动态观察模型鼠的一般状态、结肠黏膜大体和病理及电镜变化。同时检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）含量。结果大鼠的一般情况、大体病理及组织学病理及电镜变化均与人类溃疡性结肠炎类似,并且血清TNF-α、IL-2、IL-4含量变化亦与人类溃疡性结肠炎的变化基本一致。结论 TNBS可以成功诱导大鼠溃疡性结肠炎动物模型,一般情况、大体与病理表现与人UC的相似度高,有急、慢性转变过程等,而且是免疫学模型,可用于UC免疫学方面的研究。