四氢大麻酚对C57BL/6小鼠自身免疫性肝炎的保护作用

为研究大麻素成分[四氢大麻酚(tetrahydrocannabinol, THC)]对C57BL/6小鼠自身免疫性肝炎(autoimmune hepatitis, AIH)的影响,尾静脉注射质粒pCYP2D6和pcDNA3.1,腹腔重复注射四氯化碳(carbon tetrachloride, CCl4)和THC,ELISA检测自身免疫应答程度,微板法检测血清中谷丙转氨酶(alanine aminotransferase, ALT)活性,HE染色检测肝脏炎症反应程度,天狼猩红染色检测肝脏纤维化程度。结果显示,THC对由CCl4/CYP2D6引起的AIH造成的肝损伤有显著改善,而且对自身免疫应答有显著抑制作用,自身抗体和抗CYP2D6抗体水平显著降低,对于单独由CYP2D6引起的抗CYP2D6抗体能够完全抑制。THC对AIH和肝纤维化也有显著的抑制作用,且THC的抑制作用与其浓度有关。由此THC对由CCl4/CYP2D6引起的C57BL/6小鼠的AIH有显著抑制作用,并且呈剂量依赖性。由此大麻素类药物THC对AIH可能有保护作用。

Protective effect of tetrahydrocannabinol on autoimmune hepatitis in C57BL/6mice

To investigate the effect of cannabinoids (tetrahydrocannabinol, THC) on autoimmune hepatitis in C57BL/6 mice, the plasmids pCYP2D6 and pcDNA3.1 were injected intravenously and the carbon tetrachloride (CCl4) and THC were repeatedly injected intraperitoneally. The autoimmune response was detected in vivo by ELISA. The serum alanine aminotransferase (ALT) enzyme activity was measured. HE staining was used to detect liver inflammation. Liver fibrosis was detected by Sirius red staining. The results showed that THC had significant inhibitory effect on liver damage and autoimmune responses caused by CCl4/CYP2D6. Autoantibodies and anti-CYP2D6 antibodies were significantly reduced by THC. Anti-CYP2D6 antibody caused by CYP2D6 alone was completely inhibited by THC. THC also had significant inhibitory effect on autoimmune hepatitis and liver fibrosis, and the inhibitory effect depended on its concentrations. Thus, THC has a significant dose-dependent inhibitory effect on autoimmune hepatitis caused by CCl4/CYP2D6 in C57BL/6 mice, and could have a therapeutic effect on autoimmune hepatitis.