复方生地合剂对MRL/lpr小鼠Janus激酶/信号转导和转录激活因子信号通路的影响*

作者：朱博玉，陈薇薇，刘智超，常靖升，黄慧萍

单位：上海中医药大学附属市中医医院，上海 200071

引用：引用：朱博玉，陈薇薇，刘智超，常靖升，黄慧萍.复方生地合剂对MRL/lpr小鼠Janus激酶/信号转导和转录激活因子信号通路的影响[J].中医药导报,2025,31(8):41-46.

DOI：10.13862/j.cn43-1446/r.2025.08.007

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摘要：目的：探讨复方生地合剂对MRL/lpr小鼠Janus激酶（JAK）/信号转导和转录激活因子（STAT）信号通路的影响。方法：将30只MRL/lpr小鼠随机分组为模型组、复方生地合剂组、强的松组，每组10只；取10只雌性C57BL/6小鼠作为空白组。复方生地合剂组小鼠予复方生地合剂药液灌胃（27.7 g/kg），强的松组小鼠予强的松片混悬液灌胃（12.3 mg/kg），模型组、空白组小鼠予0.9%氯化钠溶液灌胃（0.3 mL/次），各组均每日给药1次，灌胃8周。观察各组小鼠一般情况、死亡情况、脾脏指数；采用酶联免疫吸附试验（ELISA）法检测血清白细胞介素-2（IL-2）、白细胞介素-17（IL-17）、抗ds-DNA、免疫球蛋白G（IgG）水平；采用Western blotting检测小鼠Janus激酶2（JAK2）、磷酸化Janus激酶2（p-JAK2）、信号转导和转录激活因子1（STAT1）和磷酸化信号转导和转录激活因子1（p-STAT1）蛋白表达；采用HE染色观察肾组织病理变化；采用免疫组化染色检测织p-JAK2阳性表达。结果：模型组、复方生地合剂组、强的松组各有1只小鼠死亡，空白组无小鼠死亡。模型组小鼠脾脏指数高于空白组（P<0.05）；复方生地合剂组、强的松组小鼠脾脏指数均低于模型组（P<0.05）。模型组小鼠血清IL-17、IgG、抗ds-DNA水平高于空白组，IL-2水平低于空白组（P<0.05）；复方生地合剂组、强的松组小鼠血清IL-17、IgG、ds-DNA水平均低于模型组（P<0.05），IL-2水平高于模型组（P＜0.05）。模型组小鼠肾组织JAK2、p-JAK2、STAT1及p-STAT1蛋白相对表达量高于空白组（P＜0.05）；复方生地合剂组、强的松组小鼠肾组织JAK2、p-JAK2、STAT1及p-STAT1蛋白相对表达量均低于模型组（P＜0.05）。模型组小鼠肾组织p-JAK2阳性表达水平高于空白组（P<0.05）；复方生地合剂组、强的松组小鼠肾组织p-JAK2阳性表达水平均低于模型组（P<0.05）。模型组肾脏病理显示系膜细胞及内皮细胞增生，大范围炎症细胞浸润；复方生地合剂组、强的松组可见少量系膜细胞及内皮细胞增生，轻微炎症细胞浸润，轻度肾小管变性。结论：复方生地合剂可能通过抑制JAK2/STAT1信号通路，抑制MRL/lpr小鼠相关炎症因子和抗体表达。

关键词：系统性红斑狼疮；复方生地合剂；蛋白酪氨酸激酶2；信号转导与转录活化因子1；MRL/lpr小鼠

Abstract：

Objective: To explore effect of compound Shengdi mixture (CSM) on janus kinase (JAK)/signal transduction and activator of transcription (STAT) in mice of systemic lupus erythematosus. Methods: Totally 30 MRL/lpr mice were randomly divided into model group, CSM group and prednisone group, with 10 mice in each group. And 10 female C57BL/6 mice were used as blank group. The mice were given CSM liquid medicine (27.7 g/kg) by gavage in CSM group, and prednisone tablet suspension (12.3 mg/kg) by gavage in prednisone group. The mice were given 0.9% sodium chloride solution by gavage (0.3 mL per time) in the model group and blank group, once a day for 8 weeks. The general situation, death and spleen index were observed. The levels of interleukin-2 (IL-2), interleukin-17 (IL-17), anti-ds-DNA and immunoglobulin G (IgG) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of janus kinase 2 (JAK2), phosphorylase JAK2 (p-JAK2), signal transduction and activator of transcription 1 (STAT1) and phosphorylase STAT1 (p-STAT1) proteins in mice. HE staining was used to observe the pathological changes of kidney tissue. Immunohistochemical staining was used to detect the positive expression of p-JAK2. Results: There was one mouse died in the model group, CSM group and prednisone group, and there was no mouse died in blank group. The model group showed higher spleen index than blank group (P<0.05). The CSM group and prednisone group showed lower spleen index than model group (P<0.05). The model group showed higher levels of serum IL-17, IgG and anti-ds-DNA than blank group, while lower level of IL-2 than blank group (P<0.05). The CSM group and prednisone group showed lower levels of serum IL-17, IgG and anti-ds-DNA than model group, while higher level of IL-2 than model group (P<0.05). The model group showed higher protein contents of JAK2, p-JAK2, STAT1 and p-STAT1 in renal tissue than blank group (P<0.05). The CSM group and prednisone group showed lower protein contents of JAK2, p-JAK2, STAT1 and p-STAT1 in renal tissue than model group (P<0.05). The model group showed higher positive expression of p-JAK2 in kidney than blank group (P<0.05). The CSM group and prednisone group showed lower positive expression of p-JAK2 in kidney than model group (P<0.05). Renal pathology in model group showed that mesangial cells and endothelial cells proliferated and inflammatory cells infiltrated in a large range. In CSM group and prednisone group, a small amount of mesangial cells and endothelial cells proliferated, with slight inflammatory infiltration and mild renal tubular degeneration. Conclusion: Compound Shengdi mixture may inhibit the expression of inflammatory factors and antibodies through inhibition of JAK2/STAT1 pathway.

Key words：systemic lupus erythematosus; compound Shengdi mixture; janus kinase 2; signal transduction and activator of transcription 1; MRL/lpr mice

发布时间：2026-01-06

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