TLR7信号通路在狼疮性肾炎发病机制中的作用
The Role of TLR7 Signaling Pathway in the Pathogenesis of Lupus Nephritis

目的：探讨TRL7信号通路对MRL-lpr狼疮性肾炎(Lupus nephritis, LN)模型小鼠相关细胞因子、蛋白表达的作用。方法：流式细胞术检测各组小鼠脾脏组织总B细胞、浆细胞和DC细胞表达；ELISA法检测各组小鼠血清IL-10、IL-21、抗C1q抗体、抗r-RNP抗体(RRNP)及B细胞激活因子(BAFF)蛋白表达。结果：流式细胞检测结果显示：与正常对照组相比，MRL-lpr模型组小鼠总B细胞及DC细胞数量无显著变化，浆细胞数量显著升高，差异具有统计学意义(P < 0.001)，在MRL-lpr模型组小鼠，与溶剂对照组相比，TRL7抑制剂组总B细胞、浆细胞及DC细胞数量均未见明显变化，差异无统计学意义(P > 0.05)；ELISA检测结果显示：与Naive小鼠相比，MRL/lpr模型组小鼠IL-10和C1q表达显著降低，差异具有统计学意义(P < 0.05)；IL-21和BAFF蛋白表达升高，差异具有统计学意义(分别是P < 0.05和P < 0.01)；RRNP表达未发生明显变化。在MRL-lpr模型组小鼠，与溶剂对照组相比，TRL7抑制剂可显著逆转IL-21和BAFF的升高(分别是P < 0.05和P < 0.01)及C1q的降低(P < 0.05)；而未显著改变IL-10和RRNP的表达(均为P > 0.05)。结论：LN小鼠体内存在细胞免疫功能紊乱，TLR7信号通路可能通过影响免疫细胞释放IL-21、C1q和BAFF等，调控LN发病进程。
Objective: To investigate the effect of TRL7 signaling pathway on the expression of cytokines and proteins related to MRL-lpr lupus nephritis (LN) model mice. Methods: Flow cytometry was performed to detect the expression of total B cells, plasma cells and DC cells in the spleen tissue of each group of mice; ELISA was performed to detect the expression of serum IL-10, IL-21, anti-C1q antibody, anti-r-RNP antibody (RRNP) and B-cell activating factor (BAFF) protein in each group of mice. Results: The results of flow cytometric assay showed that compared with the normal control group, there was no significant change in the number of total B cells and DC cells in the MRL-lpr model group mice, and the number of plasma cells was significantly higher, and the difference was statistically significant (P < 0.001). In the MRL-lpr model group mice, compared with the solvent control group, the number of total B cells, plasma cells and DC cells in the TRL7 inhibitor group did not show significant changes, and the differences were not statistically significant (P > 0.05); ELISA results showed that compared with Naive mice, IL-10 and C1q expressions were significantly lower in the MRL/lpr model group mice, and the differences were statistically significant (P < 0.05); IL-21 and BAFF protein expressions were elevated, and the differences were statistically significant (P < 0.05 and P < 0.01); RRNP expression did not change significantly. In MRL-lpr model mice, TRL7 inhibitor significantly reversed the elevation of IL-21 and BAFF (P < 0.05, P < 0.01, respectively) and the decrease of C1q (P < 0.05) compared with solvent controls; while it did not significantly alter the expression of IL-10 and RRNP (both P > 0.05). Conclusion: Cellular immune dysfunction exists in LN mice, and TLR7 signaling pathway may regulate the pathogenesis of LN by affecting the release of IL-21, C1q and BAFF