二氢杨梅素对小鼠葡聚糖硫酸钠结肠炎的干预作用

目的探讨二氢杨梅素(DMY)对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的作用效果。方法将60只Balb/C小鼠随机分为正常对照组、模型组、DMY低剂量组(50 mg·kg~(-1)·d~(-1))、DMY中剂量组(100 mg·kg~(-1)·d~(-1))、DMY高剂量组(200 mg·kg~(-1)·d~(-1))和5-氨基水杨酸组(50 mg·kg~(-1)·d~(-1)),各10只。正常对照组小鼠每日给予蒸馏水饮用,其余组小鼠给予4%DSS连续饮用7 d,诱导小鼠急性UC模型,与此同时给予对应剂量的药物灌胃治疗。7 d后处死小鼠并计算小鼠疾病活动指数(DAI)、光镜下结肠组织损伤评分(TDI),流式细胞法测定外周血中调节性T淋巴细胞(Treg)、辅助性T细胞17(Th17)占CD4+T细胞的百分比,Western blot及免疫组化法测定结肠组织中基质金属蛋白酶9(MMP 9)的表达水平。结果与正常对照组相比,模型组DAI、TDI明显升高(P<0.01),Treg/Th17比值明显降低(P<0.01),MMP 9表达升高(P<0.05)。与模型组相比,DMY低、中、高剂量组小鼠Treg/Th17比值明显升高(P<0.01),MMP 9表达降低(P<0.05),DMY中、高剂量组小鼠DAI、TDI明显降低(P<0.01),且随着治疗剂量增加,升高或降低幅度愈明显。结论 DMY可以显著缓解DSS诱导的小鼠UC炎症,且与剂量呈正相关。     

Effects of chondroitin sulfate on colitis induced by dextran sulfate sodium in rats

Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg/kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.     

Participation of mast cells in colitis inflammation induced by dextran sulfate sodium

We investigated the participation of mast cells in colitis inflammation induced by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO) activity were measured to confirm the occurrence of colitis. Rat mast cell protease (RMPCP) II levels in the serum were estimated as an index of mast cell degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), respectively. Administration of 4% DSS resulted in time-related increases in damage score, MPO activity and serum RMCP II levels, which were statistically significant at 7 and 11 days after treatment. Tissue RMCP I and RMCP II levels in the rectum were also increased significantly at 7 and 11 days, and 11 days, respectively after free drinking of 4% DSS. These results suggested that mast cells proliferated or the amount of protease per mast cell increased in the sites of inflammation induced by DSS, and that these mast cells may modulate the disorders observed in DSS-induced colitis.     

半夏泻心汤对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎影响及作用机制

目的研究半夏泻心汤对溃疡性结肠炎( UC)小鼠氧化应激损伤的影响,并探讨核转录因子 E2相关因子( Nrf2)/血红素加氧酶 -1(HO-1)通路在其中发挥的作用。方法 2023年 1―5月,小鼠自由饮用 3%葡聚糖硫酸钠( DSS)1周,建立溃疡性结肠炎模型。 60只雄性 C57BL/6J小鼠采用随机数字表法分为空白组、模型组、美沙拉嗪组( 100 mg/kg)、半夏泻心汤高、中、低剂量组( 32.76、16.38、8.19 g/kg)。造模同时灌胃给予相应药物,连续 10 d。实验结束时称量小鼠体质量、测量结肠长度并观察结肠组织病理学改变。酶联免疫法检测血清中活性氧自由基( ROS)、丙二醛(MDA)、超氧化物歧化酶( SOD)、谷胱甘肽过氧化物酶( GSH-px)变化情况; RT-PCR和蛋白质印迹法分别检测 Nrf2、HO-1、醌氧化还原酶 -1(NQO-1)的 mRNA和蛋白含量。结果空白组小鼠结肠长度、 ROS、MDA、SOD、GSH-px含量分别为( 12.53±0.94)cm、(9.39±0.76)U/mL、(4.32±0.37)nmol/L、(124.79±11.27)U/mL、(1 102.92±87.20)U/mL;模型组小鼠结肠长度、 ROS、MDA、SOD、GSH-px含量分别为( 5.63±0.45)cm、(13.30±1.47) U/mL、(7.65±0.81)nmol/L、(80.31±8.98)U/mL、(823.00±89.63)U/mL。与空白组相比,模型组小鼠体质量和结肠长度明显降低,结肠黏膜组织隐窝结构被破坏、杯状细胞减少、炎性细胞浸润明显,血清中 ROS、MDA含量明显增加,抗氧化酶 SOD、GSH-px活性明显降低, Nrf2、HO-1、NQO-1 mRNA及蛋白含量显著下降。半夏泻心汤高剂量组小鼠结肠长度、 ROS、MDA、SOD、GSH-px含量分别为( 8.97±1.20)cm、(10.49±1.04)U/mL、5.72±0.57 nmol/L、112.24±10.85 U/mL、1032.20±117.66 U/mL;半夏泻心汤中剂量组小鼠结肠长度、 ROS、MDA、SOD、GSH-px含量分别为( 8.03±0.69)cm、(11.23±1.11)U/mL、(6.47±0.30)nmol/L、(93.20±11.47)U/ mL、(993.96±96.72)U/mL;半夏泻心汤低剂量组小鼠结肠长度、 ROS、MDA、SOD、GSH-px含量分别为( 7.53±0.69)cm、(12.33±1.45)U/mL、(7.23±0.65)nmol/L、(84.89±9.07)U/mL、(891.06±86.61)U/mL。与模型组相比,半夏泻心汤干预后,小鼠体质量和结肠长度明显增加,结肠组织隐窝结构清晰且炎性细胞浸润减少,血清中 ROS和 MDA含量明显降低, SOD和 GSH-px活性明显增加,结肠组织中 Nrf2、HO-1、NQO-1 mRNA和蛋白表达亦显著提高。结论半夏泻心汤可改善 UC症状,通过调节 Nrf2/HO-1相关蛋白表达水平,进而影响氧化应激指标 ROS、MDA、SOD和 GSH-px含量,减轻结肠病理损伤程度。为半夏泻心汤开发为防治 UC药物奠定一定基础。     

乳香及其炮制品对葡聚糖硫酸钠诱导小鼠炎症性肠病的保护作用

目的 研究乳香及其炮制品对葡聚糖硫酸钠（DSS）诱导的小鼠炎症性肠病的保护作用。方法 采用DSS水溶液代替正常饮水建立炎症性肠病小鼠模型,将实验小鼠分为对照组、模型组、柳氮磺胺吡啶（300 mg/kg）组、生乳香（0.76 g/kg）组、醋乳香（0.76 g/kg）组、生乳香粪清液（0.2 mL）组、醋乳香粪清液（0.2 mL）组,分别进行给药治疗。观察和监测小鼠体质量、粪便性状、便血情况,进行疾病活动指数（DAI）评分;记录结肠长度;运用苏木精–伊红染色法（HE）观察炎症性肠病小鼠肠道组织的病理变化;酶联免疫吸附试验（ELISA）检测炎症性肠病小鼠血清中白细胞介素（IL）-4、IL-10、IL-6、IL-1β的水平。采用蛋白质免疫印迹法（Western blotting）测定炎症性肠病小鼠肠道组织中肠黏膜机械屏障蛋白的表达情况。结果 生乳香、醋乳香、生乳香粪清液组和醋乳香粪清液组均可改善DSS造成的小鼠体质量下降、粪便性状评分和便血情况,显著降低DAI评分;改善炎症性肠病小鼠肠道组织的病理状态;调节血清中的炎症因子水平;显著升高炎症性肠病小鼠肠道组织中咬合蛋白（occludin）、紧...     

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。     

Protective effects of dextran sulfate and polyvinyl sulfate against acute toxicity of paraquat in mice

The protective effects of sodium dextran sulfate (SDS) and potassium polyvinyl sulfate (PPS) against the acute toxicity of paraquat (PQ) in mice were studied. The survival rates of mice treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after PQ ingestion (200 mg/kg) were 100% or 100%, respectively. When treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) 15 or 30 min after PQ ingestion (200 mg/kg), the survival rates were 83% or 67% for SDS-treated groups and 67% or 33% for PPS-treated groups, respectively. Treatment with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after oral administration of PQ (200 mg/kg) increased the fecal excretion of PQ, decreased the urinary excretion of PQ and decreased the contents of PQ in the lung, liver and kidney. Such effects of SDS and PPS were reduced in the treatment with these drugs at 15 min after PQ. The in situ small intestinal absorption of PQ was significantly reduced in the presence of SDS or PPS. The binding of PQ to SDS or PPS was determined by an ultrafiltration method. These results indicate that SDS and PPS inhibit the gastrointestinal absorption of PQ on the basis of the increased intestinal transit of PQ and the binding of PQ to the drugs resulting in the protective effectiveness of SDS and PPS on the acute toxicity of PQ.     

灰绿黄堇总生物碱对实验性溃疡性结肠炎的作用研究

目的研究灰绿黄堇总生物碱（ACAM）对小鼠结肠炎的作用及其机制。方法实验设正常、模型、柳氮磺胺吡啶组（SASP,520mg/kg）和ACAM组（100、200、400mg/kg）。正常组小鼠饮用蒸馏水,其余组自由饮用4%葡聚糖硫酸钠（DSS）水溶液,同时分别灌胃给予溶剂或干预药物（0.2ml/10g,1次/d×7d）。记录小鼠疾病活动指数（DAI）;测定结肠组织MDA含量,SOD、MPO活性及ICAM-1、NF-κBp65表达水平。结果模型组DAI显著增高,结肠黏膜损伤严重;MDA舍量、MPO活性及ICAM-1和NF-κBp65表达明显升高。SOD活性下降（P〈0.01）。SASP520mg/kg能明显逆转上述改变;ACAM100mg具有相似的作用。结论ACAM可能通过抗氧自由基作用,抑制炎性细胞活化、迁移及NF-κB激活,缓解小鼠结肠炎性反应。     

Efficacy of dibenzoylmethane derivatives in protecting against endoplasmic reticulum stress and inhibiting nuclear factor kappa B on dextran sulfate sodium induced colitis in mice

We recently reported that some dibenzoylmethane (DBM) derivatives have a protective effect against endoplasmic reticulum (ER) stress and inhibit nuclear factor kappa B (NF-κB). The aim of this study was to evaluate the effect of DBM derivatives against dextran sulfate sodium (DSS)-induced colitis in mice. The DBM derivatives used in this study were 4,4'-dibromodibenzoylmethane that protects against ER stress, and, 4,4'-dichlorodibenzoylmethane that protects against ER stress and inhibits NF-κB. In each group, the presence of faecal occult blood, the disease activity index score (DAI score) and intestinal length were examined. Both of the DBM derivatives with protective effects against ER stress significantly improved occult bleeding of the colitis induced by DSS. The 4,4'-dichlorodibenzoylmethane significantly reduced the DAI score and inhibited the shortening of colon length, but the 4,4'-dibromodibenzoylmethane did not. These findings suggest that both the protective effect against ER stress and inhibitory effect on NF-κB are needed in the treatment of DSS-induced colitis. Therefore, the effect of 4,4'-dichlorodibenzoylmethane maybe beneficial in the therapeutic regulation of ulcerative colitis.     

龙胆苦苷对结肠炎小鼠的治疗作用

目的探究龙胆苦苷对结肠炎小鼠的治疗作用。方法采用2,4,6-三硝基苯磺酸(TNBS)-乙醇溶液诱导结肠炎小鼠模型,测定龙胆苦苷给药后对小鼠体质量、结肠指数、胸腺质量、结肠组织中髓过氧化物酶(MPO)活性以及血清炎症细胞因子TNF-α和IL-8的影响,并通过免疫组化法观察龙胆苦苷对小鼠结肠组织中环氧合酶-2(COX-2)蛋白表达的影响。结果给药1周后,龙胆苦苷各剂量组小鼠体质量与模型组相比显著改善;小鼠结肠指数、结肠组织中MPO活性以及炎性细胞因子TNF-α和IL-8与模型组相比均显著降低(P<0.05);免疫组化结果显示,龙胆苦苷能降低结肠炎小鼠组织中环氧合酶-2(COX-2)的蛋白表达。结论龙胆苦苷能修复TNBS-乙醇溶液诱导的小鼠结肠损伤,对小鼠结肠炎有显著的治疗作用。     

Embelin ameliorates dextran sodium sulfate-induced colitis in mice

Embelin has been used to treat fever, inflammatory diseases, and a variety of gastrointestinal ailments for thousands of years. Although reports indicate that embelin has anti-inflammatory and anti-tumor effects, its effects on ulcerative colitis have not been previously explored. The purpose of the present work was to evaluate the anti-inflammatory effect of embelin on dextran sulfate sodium (DSS)-induced colitis. Experimental colitis was induced in BALB/c mice by dissolving 5% DSS in their drinking water for 7days. Embelin (10, 30 or 50mg/kg body weight) was administrated daily per oral route for 7days. Embelin significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. Embelin administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size. Histological examinations indicated that embelin suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, embelin inhibited the abnormal secretions and mRNA expressions of pro-inflammatory cytokines, such as, TNF-α, IL-1β, and IL-6. These results suggest that embelin has an anti-inflammatory effect at colorectal sites that is due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD).     

Role of group IIA phospholipase A2 in rat colitis induced by dextran sulfate sodium

Although group IIA phospholipase A(2) has been suggested to be implicated in inflammatory bowel disease, its pathophysiological role in colitis remains unclear. We investigated whether group IIA phospholipase A(2) had pro-inflammatory roles in dextran sulfate sodium-induced colitis in the rat. Secretory phospholipase A(2) activity was markedly increased in the distal colon with two peaks. Strong immunostaining for group IIA phospholipase A(2) was found in subepithelial tissue and lamina propria at early stage and in deeper tissues of the erosion area at later stage. Treatment with a specific group IIA phospholipase A(2) inhibitor, S-3013/LY333013 (methyl[[3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)]-1H-indol-4yl]oxy) acetate), reduced erosion area, shortening of colon and colonic inflammation, and strongly inhibited the increase in secretory phospholipase A(2) activity and moderately reduced myeloperoxidase activity in the colon in vivo, while eicosanoid levels were not affected. Marked group IIA phospholipase A(2) expression in the erosion area and the improvement of colitis by the group IIA phospholipase A(2) inhibitor strongly suggest that this enzyme plays pro-inflammatory roles in this colitis model.     

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

BACKGROUND AND PURPOSE: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-kappaB (NF-kappaB) activity in macrophages. In the present study, we investigated the effect of gamma-oryzanol (gamma-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of gamma-ORZ, and ferulic acid (FA), a possible metabolite of gamma-ORZ in vivo, on a model of colitis in mice. EXPERIMENTAL APPROACH: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-kappaB activity in colitis tissue. KEY RESULTS: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-kappaB p65 nuclear translocation and inhibitory protein of nuclear factor-kappaB-alpha degradation levels were significantly increased in DSS-induced colitis tissues. gamma-ORZ (50 mg kg(-1) day(-1) p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that gamma-ORZ and CAF had strong antioxidant effects comparable to those of alpha-tocopherol. CONCLUSIONS AND IMPLICATIONS: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-kappaB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates.     

Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice

The anti-inflammatory effect of three flavonoids from the root of Scutellaria baicalensis (baicalein, baicalin and wogonin) was evaluated in a murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Baicalein, but not baicalin or wogonin, given orally at 20 mg/kg for ten days, ameliorates all the considered inflammatory symptoms of the induced colitis, such as body weight loss, blood haemoglobin content, rectal bleeding and other histological and biochemical parameters. The effect of baicalein was similar to that of sulfasalazine, the reference drug given at 50 mg/kg.     

Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice

Probiotics have been used to treat human gastrointestinal inflammations including inflammatory bowel disease (IBD). However, the exact mechanisms by which probiotics act to protect against intestinal inflammation have yet to be fully elucidated. The aim of this study was to evaluate anti-inflammatory effects of Lactococcus lactis subsp. cremoris FC using in vivo and in vitro inflammation models. Colitis was induced in C57BL/6 mice by administration of 3% dextran sulfate sodium to drinking water. In the cellular level assessment, a gut inflammation model with the co-culture system consisting Caco-2 cells and RAW264.7 cells stimulated by LPS was used. Administration of L. lactis subsp. cremoris FC significantly ameliorated shortening of colon length and histological score of the colon in DSS-induce colitis mice. In addition, the treatment of L. lactis subsp. cremoris FC improved the aberrant mRNA expression in inflamed tissue near to control level through notable suppression of TNF-α (P < 0.05), IFN-γ (P < 0.05), IL-6, iNOS, and MIP-2 mRNA expression. In addition, in a gut inflammation model, treatment with L. lactis subsp. cremoris FC resulted in significant down-regulation of IL-8 mRNA expression in Caco-2 cells and inhibition of NF-κB nuclear translocation in RAW264.7 cells. Our findings indicate that administration of L. lactis subsp. cremoris FC improves negative effects of DSS-induced colitis in mice through the inhibition of inflammatory cell infiltration.     

High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis

Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1⁺ myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c⁺ CD103⁻ CD11b⁺ DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c⁺ CD103⁻ CD11b⁺ DCs, but also decreased CD11c⁺ CD103⁺ CD11b⁺ in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis.     

Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica, a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis(UC)). Due to its poor aqueous solubility, a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) nanoformulation with smaller size, higher negative zeta potential and drug content, and excellent stability was developed. The appearance of BR-SMEDDS remained clear and transparent, and transmission electron microscopy showed microemulsion droplets to be spherical with homogeneous distribution. Pharmacokinetic parameters indicated that oral bioavailability was greatly improved by BR-SMEDDS as compared with aqueous suspension. Meanwhile, the anti-colitis activity of BR-SMEDDS was evaluated on dextran sodium sulfate (DSS)-induced colitis mice model. The result illustrated that the nano-formation significantly reduced the body weight loss, recovered colon length, decreased disease activity index and microscopic score, regulated immune-inflammatory cytokines, diminished oxidative stress and repressed the colonic expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) proteins. Our findings demonstrated for the first time that BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway. The BR nano-formulation was superior to BR suspension and sulphasalazine, in treating experimental UC, and exhibited similar effect with azathioprine, with much smaller dosage. The enhanced anti-UC effect of BR might be intimately associated with the improved pharmacokinetic property by SMEDDS. The developed nano-delivery system might thus be a promising candidate for colitis treatment.     

黄连总碱对实验性溃疡性结肠炎的作用研究

目的:研究黄连总碱(TAL)对小鼠结肠炎的作用及其机制。方法:实验设正常、模型、柳氮磺胺吡啶组(SASP,520mg/kg)和TAL组(150mg/kg)。正常组小鼠饮用蒸馏水,其余组自由饮用4%葡聚糖硫酸钠(DSS)水溶液,同时分别灌胃给予溶剂或干预药物(0.2ml/10gwt,1次/d×7d)。记录小鼠疾病活动指数(DAI);测定结肠组织MDA含量,SOD、MPO活性及ICAM鄄1、NF鄄κBp65表达水平。结果:模型组DAI显著增高,结肠粘膜损伤严重;MDA含量、MPO活性及ICAM鄄1和NF鄄κBp65表达明显升高,SOD活性下降(P<0.01)。SASP520mg/kg能明显逆转上述改变;TAL150mg/kg具有相似的作用。结论:TAL可能通过抗氧自由基作用,抑制炎性细胞活化、迁移及NF鄄κB激活,缓解小鼠结肠炎症。     

Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium‐induced colitis in mice

Ulcerative colitis is a major form of inflammatory bowel disease and increases the risk of the development of colorectal carcinoma. The anti‐inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) make them promising tools for treating immune‐mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSC has hampered the use of bone marrow and umbilical cord blood derived MSC in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly‐derived umbilical MSC (UMSC) on dextran sulfate sodium‐induced colitis in mice. The severity of colitis in mice was assessed using bodyweight loss, stool consistency, rectal bleeding, colon shortening and haematological parameters. Colonic myeloperoxidase and pro‐inflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 and inducible nitric oxide synthase in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly‐derived UMSC significantly diminished the severity of colitis, reduced histolopathological score, and decreased myeloperoxidase activity and cytokines levels. Furthermore, the UMSC markedly decreased the expression of cyclooxygenase 2and inducible nitric oxide synthase in the colon. In addition, transplantation of UMSC reduced intestinal permeability and upregulated the expression of tight junction proteins. These results show that the anti‐inflammation and regulation of tight junction proteins by Wharton's jelly‐derived UMSC ameliorates colitis.