CAJ | 학술논문

目的：观察血吸虫病肝纤维化小鼠模型中白介素22（IL-22）及其受体（IL-22R1）的表达状况，并对与IL-22相关的肝星状细胞（HSC）衰老机制进行探讨。方法建立血吸虫病肝纤维化小鼠模型，按感染后第4、6、8周及12周时间点取材，行生化功能检测、HE染色和Masson染色、β-半乳糖苷酶染色检测HSC衰老状况、ELISA检测肝组织中IL-22蛋白水平、荧光定量PCR检测肝组织中IL-22及IL-22R1mRNA表达水平，另设未感染小鼠为对照组。结果感染后第8、12周时血清中丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平较对照组明显增高（P均＜0.05）。肝组织中IL-22蛋白于感染后第4、6周时表达较对照组明显增加（P均＜0.05），感染后第8周时，其表达水平较前下降，第12周时仍维持在较低水平，较第4、6周差异均有统计学意义（P均＜0.01）。IL-22mRNA动态变化与蛋白水平一致，感染后第4周时表达升高，第6周时达高峰，与对照组比较差异均有统计学意义（P均＜0.05），第8、12周表达持续下降，较第6周差异均有统计学意义（P均＜0.05）。IL-22R1mRNA表达随病程进展逐渐升高，于12周时达高峰，较对照组、第6周差异均有统计学意义（P均＜0.05）。检测发现HSC衰老，随着IL-22在晚期病程中下降，HSC衰老减少。结论 IL-22及其受体参与血吸虫病肝纤维化病程进展，早期作为炎症因子之一，参与炎症反应；至肝纤维化病程后期，可部分通过诱导HSC衰老，限制肝纤维化发展。
목적：관찰혈흡충병간섬유화소서모형중백개소22（IL-22）급기수체（IL-22R1）적표체상황，병대여IL-22상관적간성상세포（HSC）쇠로궤제진행탐토。방법건립혈흡충병간섬유화소서모형，안감염후제4、6、8주급12주시간점취재，행생화공능검측、HE염색화Masson염색、β-반유당감매염색검측HSC쇠로상황、ELISA검측간조직중IL-22단백수평、형광정량PCR검측간조직중IL-22급IL-22R1mRNA표체수평，령설미감염소서위대조조。결과감염후제8、12주시혈청중병안산안기전이매화천동안산안기전이매수평교대조조명현증고（P균＜0.05）。간조직중IL-22단백우감염후제4、6주시표체교대조조명현증가（P균＜0.05），감염후제8주시，기표체수평교전하강，제12주시잉유지재교저수평，교제4、6주차이균유통계학의의（P균＜0.01）。IL-22mRNA동태변화여단백수평일치，감염후제4주시표체승고，제6주시체고봉，여대조조비교차이균유통계학의의（P균＜0.05），제8、12주표체지속하강，교제6주차이균유통계학의의（P균＜0.05）。IL-22R1mRNA표체수병정진전축점승고，우12주시체고봉，교대조조、제6주차이균유통계학의의（P균＜0.05）。검측발현HSC쇠로，수착IL-22재만기병정중하강，HSC쇠로감소。결론 IL-22급기수체삼여혈흡충병간섬유화병정진전，조기작위염증인자지일，삼여염증반응；지간섬유화병정후기，가부분통과유도HSC쇠로，한제간섬유화발전。
Objective To investigate the dynamic expressions of interleukin-22(IL-22),Interleukin-22 receptor 1(IL-22R1),and hepatic stellate cells(HSC)senescence in mice with Schistosoma japonicum infection. Methods A murine model of S. japonicum infection was established and the serum samples and liver tissues were collected 4,6,8,12 weeks post-infection. The serum samples were detected for the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST). The pathological changes and proliferation of hepatic collagen fibers in the liver tissue were observed after HE staining and Masson staining. The HSC senescence in fibrotic livers was determined by the detection of senescence-associatedβ-galactosidase(SA-β-Gal). Sandwich ELISA was used to measure the expressions of IL-22,and Real-time PCR was used to test the mRNA levels of IL-22 and IL-22R1. The control group without S. japonicum infection was set up. Results The serum levels of ALT and AST signifi-cantly increased 8 weeks and 12 weeks after the infection(vs. 0 week,all P<0.05). The level of IL-22 increased 4 weeks and 6 weeks after the infection(vs. 0 week,both P<0.05),but reduced 8 weeks post-infection,and was even lower 12 weeks post-in-fection(vs. 4 weeks and 6 weeks,both P<0.01). Being consistent with the dynamic expression of IL-22 protein,the mRNA ex-pression of IL-22 began to increase 4 weeks and reached the peak 6 weeks after the infection(vs. 0 week,both P<0.05),and continuously declined 8 weeks and 12 weeks post-infections(vs. 6 weeks,both P<0.05). The increase of the expression of IL-22R1 mRNA was correlated with the progression of fibrosis,and the peak was in 12 weeks post-infections(vs. 0 week and 6 weeks,both P<0.05). The number of senescence-associated beta-galactosidase-positive HSCs was reduced with the decreasing expression of IL-22 in the advanced liver fibrosis. Conclusion IL-22 and IL-22R1 are involved in the pathogenesis of schistoso-miasis liver fibrosis. As an inflammation factor,IL-22 significantly increases in the early stage of fibrosis. The expression of IL-22 decreases in the late stage of fibrosis,which may contribute to HSC senescence and restrict liver fibrosis.