利用FAP动物模型观察小檗碱对肠道息肉组织中巨噬细胞分型的影响

Effect of berberine on macrophage phenotypes of intestinal polyps using FAP animal models

目的观察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巨噬细胞分型的影响,探讨其治疗FAP的作用机制。方法 SPF级4周龄Apc(Min/+)小鼠20只,随机分为小檗碱组和对照组,0.1%的小檗碱混入饮水中给药。连续给药12周后处死小鼠,免疫组织化学法观察息肉组织中巨噬细胞标志物F4/80、M1型巨噬细胞标志物诱导型一氧化氮合酶(i NOS)、M2型巨噬细胞标志物巨噬细胞甘露糖受体(MR)的表达情况;real-time PCR检测i NOS、MR和白介素10(IL-10)mRNA表达。结果小檗碱组肠道息肉总数较对照组显著降低(t=16.727,P=0.001)。小檗碱组肠道息肉间质中F4/80表达较对照组明显减少(t=5.327,P=0.043),i NOS表达较对照组显著增加(t=7.335,P=0.004),而MR表达较对照组明显减少(t=5.634,P=0.016)。小檗碱组i NOS mRNA表达较对照组明显增加(t=7.827,P=0.035),MR、IL-10mRNA表达较对照组明显减少(t=6.923,P=0.039;t=8.135,P=0.026)。结论小檗碱可能通过改变Apc(Min/+)小鼠肠道息肉组织中巨噬细胞的分型,从而发挥抑制息肉生长的作用。

Objective To observe the effect of berberine on the phenotype of macrophages in the intestinal polyp tissue of Apc（ Min / ＋）mice of familial adenomatous polyposis（ FAP） animal model and explore the mechanism of treating FAP. Methods Twenty 4-week-old SPF Apc（ Min / ＋）mice were randomly divided into the control group and berberine group（ administrated with berberine of 0. 1% in drinking water）. Mice were sacrificed after being continuously administrated for 12 weeks. Expressions of macrophage marker F4 /80, M1 macrophage marker inducible nitric oxide synthase-2（ i NOS）, and M2 macrophage marker macrophage mannose receptor（ MR） in the polyp tissue were detected by the immunohistochemistry method. The mRNA expressions of i NOS, MR, and IL-10 were detected by the real-time PCR. Results Compared with the control group, the total number of intestinal polyps of the berberine group was significantly smaller（ t = 16. 727, P = 0. 001）; the expression of F4 /80 in stroma of intestinal polyps significantly decreased（ t = 5. 327, P = 0. 043）; the expression of i NOS significantly increased（ t= 7. 335, P = 0. 004）; the expression of MR significantly decreased（ t = 5. 634, P = 0. 016）; the mRNA expression of i NOS significantly increased（ t = 7. 827, P = 0. 035）; and the mRNA expressions of MR and IL-10 significantly decreased（ t = 6. 923, P = 0. 039; t = 8. 135, P = 0. 026）. Conclusion Berberine can inhibit the growth of intestinal polyps of Apc（ Min / ＋）mice by altering the phenotype of macrophages in the intestinal polyp tissue.