同型半胱氨酸调控MEK-ERK-MLCK通路影响结肠炎大鼠肠黏膜通透性的实验研究

目的探讨同型半胱氨酸(homocysteine,Hcy)是否通过调控MEK-ERK-MLCK通路影响结肠炎大鼠肠黏膜通透性的机制。方法 SD大鼠分为4组,A组为正常对照组(NS皮下注射+NS灌肠),B组为正常对照+Hcy注射组(Hcy皮下注射+NS灌肠),C组为TNBS模型组(NS皮下注射+TNBS灌肠),D组为TNBS模型+Hcy注射组(Hcy皮下注射+TNBS灌肠)。建立高Hcy血症的实验性结肠炎大鼠模型,实验结束时取大鼠结肠组织病理学检查,并进行结肠匀浆检测MPO活性,采用Western blot方法检测大鼠小肠组织中MEK、ERK、p-ERK、MLCK、p-MLCK的蛋白表达水平,采用RT-q PCR方法检测大鼠小肠组织中MLCK mRNA表达。结果与正常对照组及模型对照组相比,TNBS模型+Hcy皮下注射组大鼠DAI及HI评分增高,结肠匀浆MPO活性增高,小肠黏膜组织MEK、ERK、p-ERK、MLCK、p-MLCK蛋白表达水平增加,MLCK mRNA相对表达量增加。结论 Hcy增加实验性结肠炎大鼠肠黏膜通透性,可能与调控MEK-ERKMLCK信号通路有关。     

4-氨基水杨酸口服结肠定位包衣片的体内药效学研究(英文)

目的：评价自制的4-氨基水杨酸口服结肠定位包衣片在大鼠体内的药效学。方法：以2,4,6-三硝基苯磺酸(TNBS)的乙醇溶液灌肠,制作溃疡性结肠炎大鼠模型。将大鼠随机分为7组：健康对照组,TNBS对照组,TNBS+低剂量(包衣片)组,TNBS+中剂量(包衣片)组,TNBS+高剂量(包衣片)组,TNBS+柳氮磺吡啶(SASP)组,TNBS+中剂量非包衣片组。大鼠连续给药5 d后,对结肠部位的大体形态学改变、组织学损伤以及组织髓过氧化物酶(MPO)活性进行评分或测定,评价4-氨基水杨酸(4-ASA)结肠定位包衣片在大鼠体内的药效学。结果：以TNBS灌肠可一次性制作大鼠溃疡性结肠炎模型。与4-ASA非包衣片组相比,包衣片组或SASP组显示,给药后动物结肠的大体形态改变评分、组织损伤评分及MPO活性均有所降低；高剂量组对各指标的影响与SASP无显著差异(P>0．05)。结论：与非包衣片比较,自制的4-氨基水杨酸口服结肠定位包衣片在治疗大鼠溃疡性结肠炎方面有更好的疗效。     

环孢素A对DSS结肠炎小鼠肠黏膜通透性影响及其机制的研究

目的探讨环孢素A(CsA)对葡聚糖硫酸钠(DSS)结肠炎小鼠肠黏膜通透性的影响及作用机制。方法 C57BL/6J小鼠(6～8周龄、体质量20 g±2 g、♂),实验分为正常对照组(饮用无菌蒸馏水+腹腔注射0.9%NS)、DSS模型组(DSS溶液+腹腔注射0.9%NS)、环孢素A组(DSS溶液+腹腔注射CsA)。小鼠自由饮用5%DSS溶液1周制备结肠炎模型,环孢素A(0.025 mg.g-1)腹腔注射给药,每天1次,共7 d。每日行DAI评分,实验结束后取结肠进行HE染色评分,结肠匀浆检测MPO活性、TNF-α、IFN-γ、IL-13和IL-17水平,另取小鼠小肠黏膜进行透射电镜检查和肌球蛋白轻链激酶(MLCK)活性测定,采用Evans blue和异硫氰酸荧光素-葡聚糖(FITC-D)方法检测小肠黏膜通透性。结果与正常对照组比较,模型对照组小鼠1周后出现明显体重减轻、便血和腹泻,DAI评分和HI评分增高,同时结肠黏膜MPO活性明显增高。电镜检查小鼠回肠黏膜上皮绒毛萎缩、排列不规则,细胞间连接复合体缩短、变宽,细胞间隙扩大,小肠黏膜通透性增高。小鼠结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度增高,小肠黏膜中MLCK活性明显增高。与DSS模型组比较,环孢素A组小鼠DAI评分和HI评分明显降低,结肠黏膜MPO活性减低,回肠黏膜上皮细胞绒毛排列整齐,小肠黏膜通透性降低,小肠黏膜MLCK活性和结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度降低。结论环孢素A具有明显的抗DSS小鼠结肠炎作用,机制可能与通过调控MLCK表达,改善肠黏膜通透性有关。     

溃结康对三硝基苯磺酸诱导大鼠炎症性肠病的作用研究

目的 观察溃结康经灌肠给药对三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)诱导的炎症性肠病动物模型的作用,以明确溃结康对炎症性肠病的治疗作用,为探索药物应用于克罗恩病治疗的可行性。方法 采用TNBS灌肠的方法诱导大鼠溃疡性结肠炎模型,观察溃结康灌肠给药对大鼠疾病活动指数(DAI)评分、血清干扰素-γ(IFN-γ)、白介素-l(IL-1)、白介素-4(IL-4)、白介素-10(IL-10)和肠黏膜中谷氨酰胺(Glutamine,Gln)的含量的影响,并观察药物对大鼠结肠组织损伤评分以及病理学的影响。结果 TNBS诱导的结肠炎模型可引起动物体质量下降,肉眼血便或便潜血阳性,DAI评分增高,血清IFN-γ,IL-1升高,肠黏膜Gln降低,溃结康不同剂量组灌肠给药可改善TNBS引起的DAI评分增高以及降低血清IFN-γ、IL-1水平,升高肠黏膜Gln,缓解结肠炎组织学变化,其中尤以溃结康高剂量组作用更为明显。结论 溃结康灌肠给药对缓解TNBS诱导结肠炎模型有一定治疗作用。     

褪黑激素调节巨噬细胞功能减轻结肠免疫损伤

目的:研究褪黑素(MT)对大鼠结肠免疫损伤的影响及与巨噬细胞功能的关系.方法:利用2,4,6-三硝基苯磺酸(TNBS)和乙醇灌肠制备大鼠结肠炎模型.实验设正常对照组、模型对照组、5-氨基水杨酸给药组(100 mg/kg)和MT给药组(2.5,5.0,10.0 mg/kg),每大灌肠给药一次,从制备模型d 7开始共21 d.测定结肠粘膜损伤指数(CMDI)、粘膜病理组织学评分(HS)、粪便隐血实验(OBT)和髓过氧化物酶(MPO)、IL-1、TNF-α、NO水平.结果:大鼠经TNBS和乙醇处理后CMDI、HS、OBT和MPO水平以及结肠和血浆中IL-1、TNF-α和NO水平明显高于正常,MT可不同程度逆转上述变化,减轻大鼠结肠免疫损伤.结论:MT灌肠能减轻结肠炎大鼠粘膜损伤,此与MT调节巨噬细胞功能有关.     

N-乙酰半胱氨酸对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎的保护作用

目的观察N-乙酰半胱氨酸(NAC)灌肠对小鼠急性溃疡性结肠炎的作用。方法5%葡聚糖硫酸钠(DSS)自由饮用7 d诱导小鼠急性溃疡性结肠炎,同时予以生理盐水(NS)、5-氨基水杨酸(5-ASA)、NAC保留灌肠,观察小鼠体重、粪便性状、隐血便血,计算疾病活动度(DAI)积分,检测结肠长度、结肠过氧化物酶(MPO)活性、血清过氧化物歧化酶(SOD)活力和丙二醛(MDA)含量及肠黏膜病理改变。结果NAC组小鼠隐血、便血、体重下降、DAI积分、病理改变等均好于模型组、NS组(P<0.05),与5-ASA组疗效相似。NAC组SOD活力高于模型组,MPO活性、MDA含量则低于模型组(P<0.05)。结论NAC对DSS诱导的小鼠急性溃疡性结肠炎黏膜损伤有保护作用,其机制可能与抗氧化应激有关。     

大鼠急性肠炎早期核因子-κB活化以及吡咯烷二硫氨基甲酸的抗炎作用

目的 :探讨NF κB在三硝基苯磺酸 (TNBS) 乙醇所致的大鼠结肠炎的早期活化情况 ;吡咯烷二硫氨基甲酸 (PDTC)在该模型中的抗炎作用。方法 :TNBS 乙醇灌肠建立大鼠急性结肠炎的模型 ,造模前30min经腹腔分别注射不同剂量的PDTC(1 0 ,2 5 ,50 ,1 0 0mg·kg- 1) ,设立空白对照 ,模型对照组。造模后 4h处死大鼠 ,观察结肠大体形态、湿干比及组织学改变 ,EMSA法测定NF κB的DNA结合活性 ,并检测组织中MPO、SOD、MDA变化。结果 :TNBS 乙醇造模后大鼠结肠组织中NF κB早期活化 ,PDTC能减轻TNBS 乙醇所致炎症 ,湿干比下降 ,组织学评分减少 ,MPO ,MDA值下降 ,与所用剂量正相关 ,但上述作用不通过阻断NF κB途径。结论 :NF κB在TN BS 乙醇结肠炎早期迅速活化 ,可能是机体一种早期抗损伤的自我防御事件 ,PDTC能够在早期减轻TN BS 乙醇性结肠炎     

美洲大蠊提取物Ento-A对湿热型溃疡性结肠炎模型大鼠的改善作用研究

目的:研究美洲大蠊提取物Ento-A对湿热型溃疡性结肠炎(UC)模型大鼠的改善作用。方法:将70只大鼠随机分为正常对照组(n=8)和造模组(n=62),造模组大鼠采用高糖高脂、辛辣饮食联合2,4,6-三硝基苯磺酸灌肠法复制湿热型UC动物模型。将造模成功的48只大鼠随机分为模型对照组、美沙拉嗪组(300 mg/kg)、肠炎宁(300 mg/kg)和Ento-A低、中、高剂量组(50、100、200 mg/kg,以提取物计),每组8只。正常对照组和模型对照组大鼠灌胃生理盐水,其余各组大鼠灌胃相应药物,每天1次,连续给药14 d。末次给药后,对大鼠疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)及病理组织学(HS)进行评分,测定大鼠脾指数、肝指数和结肠指数,并采用酶联免疫吸附法测定大鼠血清中白细胞介素8(IL-8)、IL-17、超氧化物歧化酶(SOD)、丙二醛(MDA)水平和结肠组织中IL-2、前列腺素E2(PGE2)、髓过氧化物酶(MPO)水平。结果:与正常对照组比较,模型对照组大鼠DAI评分、CMDI评分、HS评分、结肠指数以及血清中IL-8、IL-17、MDA水平和结肠组织中MPO、PGE2水平显著升高(P<0.01),血清中SOD水平和结肠组织中IL-2水平显著降低(P<0.01)。与模型对照组比较,Ento-A高剂量组大鼠DAI评分、CMDI评分及血清中IL-17、MDA水平和结肠组织中PGE2水平显著降低(P<0.05或P<0.01),血清中SOD水平和结肠组织中IL-2水平显著升高(P<0.01);Ento-A中剂量组大鼠CMDI评分、HS评分以及血清中IL-8、IL-17、MDA水平和结肠组织中PGE2、MPO水平显著降低(P<0.05或P<0.01),结肠组织中IL-2水平显著升高(P<0.01);Ento-A低剂量组大鼠HS评分以及血清中IL-17、MDA水平和结肠组织中MPO、PGE2水平显著降低(P<0.05或P<0.01),血清中IL-2水平显著升高(P<0.01)。结论:美洲大蠊提取物Ento-A可能通过调节免疫系统平衡、减少炎症损伤,发挥其对湿热型UC模型大鼠的改善作用。     

甘草甲醇提取物FM100对小鼠溃疡性结肠炎的药效学研究

目的观察甘草甲醇提取物FM100对小鼠溃疡性结肠炎的作用。方法用三硝基苯磺酸钠(TNBS)和乙醇制造小鼠溃疡性结肠炎模型,空白对照组和TNBS模型组灌胃等容量生理盐水,阳性对照组灌胃地塞米松0.2mg/kg,FM100大、中、小剂量组分别灌胃FM100300mg/kg、200mg/kg、100mg/kg,连续灌胃14d。观察小鼠体质量变化、腹泻、结肠黏膜组织形态学、脾脏指数及髓过氧化物酶(MPO)活力等指标。结果甘草甲醇提取物FM100可不同程度地改善TNBS/乙醇所致溃疡性结肠炎小鼠体质量下降和腹泻症状,明显降低结肠黏膜粘连及其溃疡分值和脾脏指数,但可增高MPO活力(P<0.05或P<0.01)。结论甘草甲醇提取物FM100对小鼠溃疡性结肠炎有较好的改善作用,能减轻结肠局部的病理性损伤。     

泻痢消片治疗实验性结肠炎的研究

目的考察泻痢消片对大鼠实验性结肠炎的保护作用。方法雄性SD大鼠随机分为6组,每组10只。除空白对照组外,其他组用2,4-二硝基氯苯和醋酸灌肠的方法制备大鼠结肠炎模型。泻痢消高、中、低剂量组分别给予泻痢消溶液0.28,0.56,1.12 g.kg-1,阳性对照组给予柳氮磺吡啶(0.27 g.kg-1),造模次日开始给药,每天1次,连续14 d。对大鼠疾病活动指数(DAI)进行评分,测定结肠组织中核因子κBp65(NF-κBp65)表达和髓过氧化物酶(MPO)水平。结果泻痢消高、中、低剂量组能够降低大鼠DAI评分,降低结肠组织中NF-κBp65表达和MPO水平(P<0.05或P<0.01)。结论泻痢消可以减轻肠道炎症,对实验性结肠炎有良好疗效。     

己酮可可碱对2,4,6-三硝基苯磺酸肠炎模型的影响

目的 :观察己酮可可碱 (PTX)对 2 ,4 ,6 三硝基苯磺酸 (TNBS)肠炎模型影响。方法 :通过直肠给予雄性BALB/c小鼠TNBS诱导结肠炎 ,应用PTX对其进行治疗 ,6d后收集结肠标本评价结肠炎症程度 ;采用半定量RT PCR检测肠黏膜IL 18mRNA表达 ,采用免疫组织化学染色显示IL 18阳性细胞。结果 :直肠内给予BALB/c小鼠TNBS后可造成小鼠结肠炎性改变 ;PTX治疗可使小鼠疾病活动指数、结肠重量和炎症指数均显著下降 (P <0 .0 5 ) ,结肠IL 18mRNA和肠黏膜固有层表达IL 18细胞数显著下降 (P <0 .0 5 )。结论 :PTX治疗可使TNBS肠炎模型小鼠肠黏膜局部IL 18表达显著下降 ,肠炎得以减轻。     

己酮可可碱对小鼠溃疡性结肠炎NF-κB的影响

目的:观察己酮可可碱(pentoxifylline,PTX)治疗小鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用,探讨PTX对三硝基苯磺酸(TNBS)诱导的小鼠UC NF-κB的影响.方法:用TNBS局部灌肠法建立小鼠UC模型,随机分为正常组、模型组、PTX组、柳氮磺胺吡啶(SASP)组,评价疾病活动指数(DAI),观察结肠组织学损伤,用ELISA法测定结肠组织NF-κB的水平.结果:用TNBS灌肠可使小鼠结肠炎性改变;PTX治疗可使小鼠疾病活动指数、结肠黏膜大体形态学损伤评分及组织学评分、结肠黏膜组织NF-κB的表达明显下降,与SASP相比较差异无统计学意义(P＞0.05).结论:PTX对以TNBS诱发的小鼠UC有良好的治疗作用,其作用机制可能是通过抑制小鼠结肠黏膜组织NF-κB的表达而减轻其炎症性损害.     

PARP inhibition reduces acute colonic inflammation in rats

Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20-40 mg/kg) and 1,5-dihydroxyisoquinoline (4-8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E2 (PGE2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS induction was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cells infiltration in the mucosa and necrosis. Furthermore, increased MPO activity, cyclooxygenase-2 expression and PGE2 synthesis were significantly augmented after TNBS instillation. On the contrary, treatment with 1,5-dihydroxyisoquinoline significantly reduced the degree of colon injury and also caused a substantial reduction in the rise in MPO activity, in the increase of staining for cyclooxygenase-2, as well as in the up-regulation of PGE2 caused by TNBS in the colon. Although nicotinamide significantly did not reduce macroscopic damage, it decreased both MPO activity and PGE2 colonic levels. In conclusion, we demonstrated that PARP inhibition can exert beneficial effects in experimental colitis and may, therefore, be useful in the treatment of ulcerative colitis.     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

Background:

We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats.

Methods:

TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4⁺ and CD8⁺ T cells were examined by immuno-histochemistry.

Results:

When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC.

Conclusions:

Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.

     

布地奈德脂质体温敏凝胶对溃疡性结肠炎模型小鼠的药效研究

目的:研究布地奈德脂质体温敏凝胶剂(Bud-Lip-TSG)对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)致急性溃疡性结肠炎(ulcerative colitis,UC)昆明小鼠的药效作用。方法:建立DSS诱导的小鼠UC模型。实验动物分为正常对照组、模型组、阳性对照组及Bud-Lip-TSG低、中、高剂量组。测定小鼠给药前后疾病活动指数(DAI)、肠黏膜损伤评分(CMDI)、脏器指数、结肠组织病理评分,血清中IL-6、IL-10水平,结肠组织中的TNF-α、IL-10、髓过氧化酶(MPO)水平变化。结果:Bud-Lip-TSG各剂量组小鼠的DAI评分、CMDI、结肠组织病理评分、脾脏指数降低;结肠长度、结肠湿质量、结肠指数增加;各给药组结肠组织中IL-10显著升高,TNF-α水平、MPO活力显著降低,;Bud-Lip-TSG高剂量组血液中IL-6显著降低、IL-10显著升高,Bud-Lip-TSG中、高剂量组胸腺指数显著增加。结论:Bud-Lip-TSG可改善模型小鼠UC症状,对结肠黏膜有修复作用,可改善炎症因子的表达失衡状态。     

Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis

In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.     

栀子有效部位的溃疡性结肠炎活性及其化学成分研究

目的研究栀子浸膏35%和70%乙醇洗脱部位对2,4,6-三硝基苯磺酸(TNBS)/乙醇诱导的大鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用,并采用液质联用鉴定活性洗脱部位的化学成分。方法采用TNBS诱导大鼠UC模型,不同洗脱部均按生药量2.1 g·kg-1连续灌胃给药7 d,进行体质量测定,疾病活动指数(DAI)评分,结肠组织病理评分,比较各组大鼠结肠组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6 (IL-6)、白细胞介素-1β(IL-1β)水平。采用液质联用鉴定药效较好部位的化学成分。结果与模型组相比,35%洗脱部位组体质量下降明显改善,DAI和组织病理评分降低,组织中MPO、NO、MDA、TNF-α、IL-6及IL-1β含量均降低,SOD含量升高(P <0.01)。液质联用共鉴定出19个化学成分,其中11个为环烯醚萜类成分。结论栀子35%洗脱部位对UC大鼠有明显治疗作用,环烯醚萜类成分可能是其发挥作用的物质基础。     

Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats

The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200 mg/kg) was administered for 14 days, 1 day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E₂ (PGE₂) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (IκBα) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE₂, as well as the expressions of iNOS, COX-2 and NF-κB p65 proteins in the colonic mucosa, and the significant decrease in expressions of IκBα proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100 mg/kg and 200 mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the IκBα/NF-κB p65 expression.