沙利度胺对葡聚糖硫酸钠诱导的大鼠溃疡性结肠炎疗效观察
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摘要
目的:旨在观察具有免疫调节和抗血管生成作用的沙利度胺对试验性溃疡性结肠大鼠是否具有治疗效应。
方法:40只SD大鼠分为正常对照组(CON组,n=10)和实验组(n=30),实验组大鼠通过自由饮用3%葡聚糖硫酸钠(DSS)溶液建立慢性溃疡性结肠炎模型,然后再分为实验对照组(M组,n=10)、早期给药组(S1组,n=10,第8-21天给予沙利度胺)、晚期给药组(S2组,n=10,第25-38天给予沙利度胺),观察:大鼠疾病活动指数(DAI)、结肠组织损伤指数(HI)、结肠黏膜平均血管密度(MVD)和血管内微血栓形成情况,并测定血清TNF-α、VEGF浓度。
结果:与CON组的HI(1.9±1.2)、MVD(61.1±9.8)对比,M组HI(6.1±2.8,q=6.54,P<0.05)、MVD(114.0±5.0,q=13.56,P<0.05)均显著升高,但血清TNF-α水平(CON组265.4±56.8 vs M组254.4±90.8,q=0.61,P>0.05)、VEGF水平(CON组182.8±19.3 vs M组194.7±34.9,F=2.671,v1=3,v2=34,P=0.063>0.05)的差异无统计学意义。S1组(2.7±1.6,q=4.24,P<0.05)、S2组(3.0±1.7,q=3.60,P<0.05)DAI低于M组(4.7±1.8),但与M组的HI(6.1±2.8)相比S1组HI(6.0±1.7,q=0.17,P>0.05)和S2组HI(5.8±1.9,q=0.48,P>0.05)并无明显下降;4组动物血清VEGF水平差异无统计学意义(CON:182.8±19.3,M:194.8±34.9,S1:169.7±13.6,S2:169.7±15.4,F=2.671,v1=3,v2=34,P=0.063>0.05);与M组血清TNF-α水平(254.4±90.8)相比,S1组(159.3±20.7,q=4.96,P<0.05)、S2组(172.1±23.4,q=4.55,P<0.05)血清TNF-α水平下降,同样,S1组MVD(89.8±15.1,q=6.05,P<0.05)、S2组MVD( 92.6±13.6,q=5.35,P<0.05)也低于M组(114.0±5.0)。4组血管内微血栓阳性率的差异无统计学意义(CON:30.0%,M:33.3%,S1:66.7%,S2:60.0%,χ2=3.982,v=3,P≈0.263>0.05)。
结论:沙利度胺具有抗TNF-α作用和抗血管生成作用,可以降低UC大鼠的疾病活动指数,不增加血栓局部形成的风险,但对UC的组织学改善似乎没有明显的作用。
Aims: To investigate the effect of Thalidomide, which has the effect of immunomodulation and antiangiogenesis, on chronic experimental ulcerative colitis in SD rats.
METHODS: Forty SD rats were divided into normal control group(group CON, n=10) and experimental group(group E, n=30). Group E were established Chronic experimental ulcerative colitis model by drinking 3% dextran sulfate sodium(DSS) solution for freedom, and then were divided into 3 groups(model group, group M, n=10; early administration group, group S1, n=10; later administration group, group S2, n=10). Group S1 were fed with thalidomide(200mg/kg/d) from 8th to 21st by gastric perfusion, and group S2 from 25th to 38th. Estimated disease active index(DAI), histological injury index(HI) , the mean vascular density(MVD) of colonic mucosa and the risk of microthrombosis of vascular. And the level of TNF-αand VEGF in serum were assessed, too.
RESULTS: Compared to control group, model group’s HI(1.9±1.2 in group CON vs vs 6.1±2.8 in group M, q=6.54, P<0.05) and MVD(61.1±9.8 vs 114.0±5.0, q=13.56, P<0.05) increased significantly; However, the serum level of TNF-α(265.4±56.8 vs 254.4±90.8, q=0.61, P>0.05) and VEGF(182.8±19.3 vs 194.7±34.9, F=2.671, v1=3, v2=34, P=0.063>0.05) had no significant difference. DAIs in group S1 (2.7±1.6,q=4.24,P<0.05) and group S2(3.0±1.7,q=3.60,P<0.05) were less respectively than in group M (4.7±1.8). Whereas, compared to HI in group M (6.1±2.8), HI in group S1 (6.0±1.7,q=0.17,P>0.05) and group S2(5.8±1.9 , q=0.48 , P>0.05) were not decreased predominantly. The differences of serum VEGF concentration among the 4 group had not statistical significance(CON:182.8±19.3,M:194.8±34.9,S1:169.7±13.6,S2:169.7±15.4,F=2.671,v1=3 , v2=34 , P=0.063>0.05). As for serum TNF-αlevel , compared to group M(254.4±90.8), group S1(159.3±20.7,q=4.96,P<0.05) and group S2(172.1±23.4,q=4.55,P<0.05) decreased obviously. And similarly, S1’s MVD(89.8±15.1,q=6.05,P<0.05) and S2’s(92.6±13.6,q=5.35,P<0.05) MVD were lower than M’s(114.0±5.0). The distinctions of microthrombi positive rates among the 4 group had no statistic significance(χ2=3.982, v=3, P≈0.263).
CONCLUSION: Thalidomide had the effects of anti-TNF-αand antiangiogenesis on UC rats, which ameliorated the DAI. However it didn’t change the HI and did not increase the thrombosis risk in the colon mucosa.
方法:40只SD大鼠分为正常对照组(CON组,n=10)和实验组(n=30),实验组大鼠通过自由饮用3%葡聚糖硫酸钠(DSS)溶液建立慢性溃疡性结肠炎模型,然后再分为实验对照组(M组,n=10)、早期给药组(S1组,n=10,第8-21天给予沙利度胺)、晚期给药组(S2组,n=10,第25-38天给予沙利度胺),观察:大鼠疾病活动指数(DAI)、结肠组织损伤指数(HI)、结肠黏膜平均血管密度(MVD)和血管内微血栓形成情况,并测定血清TNF-α、VEGF浓度。
结果:与CON组的HI(1.9±1.2)、MVD(61.1±9.8)对比,M组HI(6.1±2.8,q=6.54,P<0.05)、MVD(114.0±5.0,q=13.56,P<0.05)均显著升高,但血清TNF-α水平(CON组265.4±56.8 vs M组254.4±90.8,q=0.61,P>0.05)、VEGF水平(CON组182.8±19.3 vs M组194.7±34.9,F=2.671,v1=3,v2=34,P=0.063>0.05)的差异无统计学意义。S1组(2.7±1.6,q=4.24,P<0.05)、S2组(3.0±1.7,q=3.60,P<0.05)DAI低于M组(4.7±1.8),但与M组的HI(6.1±2.8)相比S1组HI(6.0±1.7,q=0.17,P>0.05)和S2组HI(5.8±1.9,q=0.48,P>0.05)并无明显下降;4组动物血清VEGF水平差异无统计学意义(CON:182.8±19.3,M:194.8±34.9,S1:169.7±13.6,S2:169.7±15.4,F=2.671,v1=3,v2=34,P=0.063>0.05);与M组血清TNF-α水平(254.4±90.8)相比,S1组(159.3±20.7,q=4.96,P<0.05)、S2组(172.1±23.4,q=4.55,P<0.05)血清TNF-α水平下降,同样,S1组MVD(89.8±15.1,q=6.05,P<0.05)、S2组MVD( 92.6±13.6,q=5.35,P<0.05)也低于M组(114.0±5.0)。4组血管内微血栓阳性率的差异无统计学意义(CON:30.0%,M:33.3%,S1:66.7%,S2:60.0%,χ2=3.982,v=3,P≈0.263>0.05)。
结论:沙利度胺具有抗TNF-α作用和抗血管生成作用,可以降低UC大鼠的疾病活动指数,不增加血栓局部形成的风险,但对UC的组织学改善似乎没有明显的作用。
Aims: To investigate the effect of Thalidomide, which has the effect of immunomodulation and antiangiogenesis, on chronic experimental ulcerative colitis in SD rats.
METHODS: Forty SD rats were divided into normal control group(group CON, n=10) and experimental group(group E, n=30). Group E were established Chronic experimental ulcerative colitis model by drinking 3% dextran sulfate sodium(DSS) solution for freedom, and then were divided into 3 groups(model group, group M, n=10; early administration group, group S1, n=10; later administration group, group S2, n=10). Group S1 were fed with thalidomide(200mg/kg/d) from 8th to 21st by gastric perfusion, and group S2 from 25th to 38th. Estimated disease active index(DAI), histological injury index(HI) , the mean vascular density(MVD) of colonic mucosa and the risk of microthrombosis of vascular. And the level of TNF-αand VEGF in serum were assessed, too.
RESULTS: Compared to control group, model group’s HI(1.9±1.2 in group CON vs vs 6.1±2.8 in group M, q=6.54, P<0.05) and MVD(61.1±9.8 vs 114.0±5.0, q=13.56, P<0.05) increased significantly; However, the serum level of TNF-α(265.4±56.8 vs 254.4±90.8, q=0.61, P>0.05) and VEGF(182.8±19.3 vs 194.7±34.9, F=2.671, v1=3, v2=34, P=0.063>0.05) had no significant difference. DAIs in group S1 (2.7±1.6,q=4.24,P<0.05) and group S2(3.0±1.7,q=3.60,P<0.05) were less respectively than in group M (4.7±1.8). Whereas, compared to HI in group M (6.1±2.8), HI in group S1 (6.0±1.7,q=0.17,P>0.05) and group S2(5.8±1.9 , q=0.48 , P>0.05) were not decreased predominantly. The differences of serum VEGF concentration among the 4 group had not statistical significance(CON:182.8±19.3,M:194.8±34.9,S1:169.7±13.6,S2:169.7±15.4,F=2.671,v1=3 , v2=34 , P=0.063>0.05). As for serum TNF-αlevel , compared to group M(254.4±90.8), group S1(159.3±20.7,q=4.96,P<0.05) and group S2(172.1±23.4,q=4.55,P<0.05) decreased obviously. And similarly, S1’s MVD(89.8±15.1,q=6.05,P<0.05) and S2’s(92.6±13.6,q=5.35,P<0.05) MVD were lower than M’s(114.0±5.0). The distinctions of microthrombi positive rates among the 4 group had no statistic significance(χ2=3.982, v=3, P≈0.263).
CONCLUSION: Thalidomide had the effects of anti-TNF-αand antiangiogenesis on UC rats, which ameliorated the DAI. However it didn’t change the HI and did not increase the thrombosis risk in the colon mucosa.
引文
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