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目的探讨CYP1B1(cytochrome P450,family 1,subfamily B,polypeptide 1)缺失对成年小鼠巨噬细胞募集及组织炎症作用。方法选择6 w周龄SPF级CYP1B1基因敲除(KO)和野生型(WT)雄性小鼠,给予低脂肪(LFD)、高脂肪(HFD)饲料,喂养6 w后分别测定各组全血葡萄糖及血清胰岛素水平。利用葡萄糖耐量实验,判断糖耐量损伤情况。HE染色及免疫荧光检测小鼠附睾脂肪组织的巨噬细胞浸润情况。多重实时定量PCR(qRT-PCR)检测附睾脂肪组织及肝脏中巨噬细胞特异性蛋白(Emr1)及肿瘤坏死因子α(TNF-a)的表达水平。结果 CYP1B1敲除可以改善高脂膳食导致的胰岛素敏感性下降;在附睾脂肪组织中,CYP1B1基因缺失与高脂肪膳食均促进巨噬细胞的募集,但CYP1B1缺失抑制高脂膳食对炎症因子的诱导;在肝脏组织中,高脂膳食诱导巨噬细胞的浸润,但CYP1B1基因缺失抑制小鼠巨噬细胞浸润并下调组织炎症因子的表达。结论 CYP1B1基因缺失对高脂膳食诱导的肥胖及相关的胰岛素敏感性下降的保护作用可能是由其对炎症抑制的组织特异性决定的。
Objective To investigate the effect of cytochrome P450 (family 1, subfamily B, polypeptide 1) deletion on macrophage recruitment and tissue inflammation in adult mice. Methods Male Wistar rats with SPF grade CYP1B1 knockout (KO) and wild type (WT) at 6 weeks of age were given low fat (LFD) and high fat (HFD) feed. After 6 weeks of feeding, the levels of whole blood glucose And serum insulin levels. Use glucose tolerance test to determine the impaired glucose tolerance. HE staining and immunofluorescence detection of mouse epididymal adipose tissue infiltration of macrophages. Multiplex real-time quantitative PCR (qRT-PCR) was used to detect the expression of macrophage-specific protein (Emr1) and tumor necrosis factor-α (TNF-a) in epididymis adipose tissue and liver. Results CYP1B1 knockdown could reduce insulin sensitivity induced by high fat diet. In epididymal adipose tissue, CYP1B1 gene deletion and high fat diet promoted macrophage recruitment, but CYP1B1 deficiency inhibited the induction of inflammatory cytokines by high fat diet. In the liver tissue, high-fat diet induces macrophage infiltration, but deletion of the CYP1B1 gene inhibits macrophage infiltration in mice and down-regulates the expression of tissue inflammatory cytokines. Conclusion The protective effect of CYP1B1 deletion on the obesity induced by high-fat diet and the related decrease of insulin sensitivity may be determined by its tissue specificity of inhibiting inflammation.