首页> 中文期刊> 《中华消化杂志》 >小檗碱对 Apc(Min/+)小鼠肠道息肉组织肿瘤相关巨噬细胞的影响

小檗碱对 Apc(Min/+)小鼠肠道息肉组织肿瘤相关巨噬细胞的影响

摘要

Objective To investigate the effects of berberine on tumor-associated macrophages (TAM)and the expression of cyclooxygenase-2 (COX-2)of intestinal polyps in Apc(Min/+) mice.Methods A total of 20 Apc(Min/+) mice,four weeks old,were equally divided into the control group and the berberine group,10 in each group.The mice of the control group drank plain water,while the mice of berberine group drank water with 0.1 % berberine.After 12 weeks,all the mice were sacrificed.The intestine and colon were isolated,and the numbers of polyps were counted.The expression of F4/80,inducible nitric oxide synthase-2 (iNOS),macrophage mannose receptor (MR)and COX-2 was detected by immunohisto-chemistry method.The relative expression of COX-2 at protein level was measured by Western blotting. The t test was performed for comparison between two independent groups.Results The total number of intestinal polyps,the number of small intestinal polyps and the number of colon polyps of the berberine group (11 .50±2.05 ,10.50±1 .77 and 1 .00±0.46,respectively)were all less than those of the control group (30.63±1 .69,28.00±2.00 and 2.63±0.74,respectively),and the differences were statistically significant (t=16.727,16.952 and 3.162,P =0.001 ,0.001 and 0.010,respectively).The percentage of F4/80 positive cells in the stroma of polyps of the berberine group ((17.40 ±4.23 )%)was less than that of the control group ((31 .24±6.34)%),and the difference was statistically significant (t =5 .327, P =0.043).The percentage of iNOS positive cells in the stroma of polyps of the berberine group ((7.43± 1 .78 )%) was higher than that of the control group ((2.72±0.68)%), and the difference was statistically significant (t=7.335 ,P =0.004).The percentage of MR positive cells in stroma of polyps of the berberine group ((19.52±1 .54)%)was less than that of the control group ((12.63±0.68)%),and the difference was statistically significant (t=5 .634,P =0.016).The percentage of COX-2 positive cells in stroma of polyps of berberine group ((3.38 ± 0.51 )%)was less than that of the control group ((7.60±0.57 )%),and the difference was statistically significant (t = 7.234,P = 0.001 ).The relative expression of COX-2 at protein level of polyps of the berberine group was lower than that of the control group. Conclusion Berberine may take the role in inhibiting the growth of intestinal polyps in Apc(Min/+) mice through interfering the differentiation of TAM in polyps and suppression the expression of COX-2.%目的:探讨小檗碱对家族性腺瘤性息肉病(FAP)动物模型 Apc(Min/+)小鼠肠道息肉组织中肿瘤相关巨噬细胞(TAM)和环氧合酶-2表达水平的影响。方法将20只4周龄 Apc(Min/+)小鼠均分为小檗碱组和对照组,每组10只。对照组正常饮水。小檗碱组饮水中混入0.1%小檗碱。12周后处死小鼠,分离小肠和结肠,计数息肉数量。采用免疫组织化学法检测息肉组织中 F4/80、诱导型一氧化氮合酶(iNOS)、甘露糖受体(MR)、环氧合酶-2的表达情况。采用 Western 印迹法检测环氧合酶-2蛋白的相对表达水平。两组间比较行独立样本 t 检验。结果小檗碱组肠道息肉总数(11.50±2.05)、小肠息肉数量(10.50±1.77)、结肠息肉数量(1.00±0.46)均少于对照组(30.63±1.69、28.00±2.00、2.63±0.74),差异均有统计学意义(t =16.727、16.952、3.162,P =0.001、0.001、0.010)。小檗碱组息肉组织间质中 F4/80阳性细胞所占比例[(17.40±4.23)%]低于对照组[(31.24±6.34)%],差异有统计学意义(t=5.327,P =0.043)。小檗碱组息肉组织间质中 iNOS 阳性巨噬细胞所占比例[(7.43±1.78)%]高于对照组[(2.72±0.68)%],差异有统计学意义(t =7.335,P =0.004)。小檗碱组息肉组织间质中 MR 阳性巨噬细胞所占比例[(19.52±1.54)%]低于对照组[(12.63±0.68)%],差异有统计学意义(t=5.634,P =0.016)。小檗碱组息肉组织间质中环氧合酶-2阳性细胞所占比例[(3.38±0.51)%]低于对照组[(7.60±0.57)%],差异有统计学意义(t =7.234,P =0.001)。小檗碱组息肉组织中环氧合酶-2蛋白相对表达水平低于对照组。结论小檗碱可能通过干预 Apc(Min/+)小鼠肠道息肉组织中 TAM 的分化,抑制环氧合酶-2的表达,从而发挥抑制息肉生长的作用。

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