咪喹莫特和雷西莫特诱导系统性红斑狼疮模型小鼠的差异性研究

Comparative study of imiquimod and resiquimod-induced systemic lupus erythematosus model mice

目的探讨咪喹莫特(IMQ)和雷西莫特(R848)诱导系统性红斑狼疮(SLE)模型小鼠的差异性。方法将8周龄的Balb/c小鼠分为空白组、对照组和实验组,每组10只。对照组给予5%IMQ乳膏1.25 mg涂抹于小鼠右耳皮肤;实验组给予R848 100μg涂抹于小鼠右耳皮肤;空白组给予凡士林1.25 mg涂抹于小鼠右耳皮肤。3组小鼠每隔1天给药1次,连续给药6周。给药6周末,检测小鼠脾、肝、肾、淋巴结的脏器系数,用酶联免疫吸附实验法检测小鼠血清抗双链DNA(ds-DNA)抗体和抗核抗体(ANA)含量,用免疫印迹实验法检测脾组织ATG5和LC3Ⅱ/Ⅰ蛋白的表达。结果实验组、对照组和空白组的脾系数分别为(53.61±8.10),(4.11±0.20)和(4.21±0.40)mg·g^-1,肝系数分别为(79.41±8.02),(48.11±3.01)和(48.32±2.01)mg·g^-1,肾系数分别为(17.81±2.04),(13.42±0.71)和(13.91±0.62)mg·g^-1,淋巴结系数分别为(4.20±2.12),(6.51±0.71)和(5.81±1.12)mg·g^-1,实验组的上述指标与对照组比较,差异均有统计学意义(P<0.01或P<0.001)。实验组、对照组和空白组的抗ds-DNA抗体分别为(29.17±4.24),(28.33±1.44)和(27.68±2.81)U·L-1,ANA分别为(8.70±2.02),(7.70±1.34)和(6.68±1.12)ng·mL-1,LC3Ⅱ/Ⅰ蛋白相对表达量分别为(0.58±0.41),(0.47±0.05)和(0.14±0.06),ATG5蛋白相对表达量分别为(1.62±0.31),(1.29±0.26)和(0.80±0.04),实验组的上述指标均较对照组有升高趋势,但差异均无统计学意义(均P>0.05)。结论 R848诱导SLE小鼠模型较IMQ效果显著,对自噬蛋白作用明显。

Objective To investigate the differences between imiquimod(IMQ)and resigqimod(R848)induced systemic lupus erythematosus(SLE)model mice.Methods Eight-week-old Balb/c mice were divided into blank,controland experimental groups with 10 mice per group.Control group was given 1.25 mg of 5%IMQ cream and applied to the skin of the right ear of mice.Experimental group was given R848100μg and applied to the skin of the right ear of mice.Blank group was given 1.25 mg of petrolatum and applied to the skin of right ear of mice.Three groups were administered every other day for 6 weeks.At the end of the 6th week,the organ coefficients of the spleen,liver,kidney and lymph nodes of the mice were measured,and the contents of anti-double-stranded DNA(ds-DNA)antibodies and anti-nuclear antibodies(ANA)in the serum of the mice were measured by enzyme linked immunosorbent assay.The expressions of ATG5 and LC3Ⅱ/Ⅰprotein in spleen tissue were detected by immunoblot experiment.Results The spleen coefficients of the experimental,control and blank groups were(53.61±8.10),(4.11±0.20),(4.21±0.40)mg·g^-1,the liver coefficients were(79.41±8.02),(48.11±3.01)and(48.32±2.01)mg·g^-1,kidney coefficients were(17.81±2.04),(13.42±0.71)and(13.91±0.62)mg·g^-1,lymph node coefficients were(4.20±2.12),(6.51±0.71)and(5.81±1.12)mg·g^-1.The above-mentioned indexes of experimental group were significantly different from those in control group(P<0.01 or P<0.001).The anti ds-DNA antibodies of experimental,control and blank groups were(29.17±4.24),(28.33±1.44)and(27.68±2.81)U·L-1,ANA were(8.70±2.02),(7.70±1.34)and(6.68±1.12)ng·mL-1,the relative expression levels of LC3Ⅱ/Ⅰprotein were(0.58±0.41),(0.47±0.05)and(0.14±0.06),the relative expression levels of ATG5 protein were(1.62±0.31),(1.29±0.26)and(0.80±0.04),respectively.The above-mentioned indexes of experimental group showed an upward trend compared with those in control group,but the differences were not statistically significant(all P>0.05).Conclusion Compared with IMQ,the R848-induced SLE mouse model had a significant effect on autophagy proteins.