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黑龙江中医药大学 中医药研究院,研究生院,黑龙江省高等学校中药基本理论研究科技创新团队, 哈尔滨 150040
周琦,博士,副研究员,从事中药药理学研究,E-mail:zhouqijoejoe@163.com
* 刘树民,博士,教授,从事中药药性理论研究,E-mail:keji-liu@163.com
收稿日期:2021-08-10,
网络出版日期:2021-10-19,
纸质出版日期:2021-12-20
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周琦,孙慧娟,刘树民.穿山龙总皂苷调控巨噬细胞M1/M2极化治疗痛风性关节炎的作用机制[J].中国实验方剂学杂志,2021,27(24):92-99.
ZHOU Qi,SUN Hui-juan,LIU Shu-min.Mechanism of Total Saponins from Dioscoreae Nipponicae Rhizoma to Treat Gouty Arthritis by Regulating M1/M2 Polarization of Macrophages[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(24):92-99.
周琦,孙慧娟,刘树民.穿山龙总皂苷调控巨噬细胞M1/M2极化治疗痛风性关节炎的作用机制[J].中国实验方剂学杂志,2021,27(24):92-99. DOI: 10.13422/j.cnki.syfjx.20212340.
ZHOU Qi,SUN Hui-juan,LIU Shu-min.Mechanism of Total Saponins from Dioscoreae Nipponicae Rhizoma to Treat Gouty Arthritis by Regulating M1/M2 Polarization of Macrophages[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(24):92-99. DOI: 10.13422/j.cnki.syfjx.20212340.
目的
2
阐明巨噬细胞 M1/M2极化在尿酸钠晶体诱导大鼠痛风性关节炎(GA)模型中的作用,揭示穿山龙总皂苷治疗GA的抗炎分子机制。
方法
2
雄性SD大鼠72只,随机分为4组,分别为正常组、模型组、穿山龙总皂苷组(160 mg·kg
-1
),塞来昔布组(43.3 mg·kg
-1
),每组18只。采用单尿酸钠晶体双侧注射大鼠踝关节方法建立大鼠GA模型。苏木素-伊红(HE)染色观察大鼠踝关节滑膜组织病理学改变。免疫组化法检测踝关节滑膜组织 CD68,白细胞介素-4(IL-4),诱导型一氧化氮合酶(iNOS)和转化生长因子-
β
1
(TGF-
β
1
) 蛋白表达的变化。
结果
2
HE染色结果显示模型组造模后第3天炎症最为明显,疾病处于急性期。第5天炎症有所缓解,第8天仍有炎症表现但接近正常组。穿山龙总皂苷组和塞来昔布组均可改善滑膜组织病理表现,穿山龙总皂苷组效果更为明显。免疫组化结果显示,与正常组比较,给药3 d,5 d和8 d时模型组 CD68和iNOS表达显著升高(
P
<
0.01);与模型组比较,给药3 d时穿山龙总皂苷可明显降低CD68和iNOS表达(
P
<
0.05,
P
<
0.01),给药5 d和8 d时穿山龙总皂苷可显著降低CD68和iNOS表达(
P
<
0.01)。与正常组比较,给药3 d时,模型组IL-4和TGF-
β
1
表达显著升高(
P
<
0.01),给药5 d和8 d时,模型组IL-4表达显著降低(
P
<
0.01),给药5 d时,模型组TGF-
β
1
表达显著降低(
P
<
0.01);与模型组比较,给药5 d和8 d时,穿山龙总皂苷可显著升高IL-4和TGF-
β
1
表达(
P
<
0.01)。
结论
2
穿山龙总皂苷可通过调控巨噬细胞 M1/M2极化对GA发挥潜在治疗效果。
Objective
2
To illustrate the effect of M1/M2 polarization of macrophages on gouty arthritis models induced with monosodium urate and reveal the molecular mechanism of total saponins from Dioscoreae Nipponicae Rhizoma to treat gouty arthritis.
Method
2
A total of 72 male SD rats were randomly divided into four groups: normal group, model group, total saponin group (160 mg·kg
-1
), celecoxib group (43.3 mg·kg
-1
), with 18 rats in each group. Gouty arthritis models were induced by injecting monosodium urate into ankle joints bilaterally. Histopathology changes of ankle joints were observed by hematoxylin-eosin(HE) staining. Immunohistochemistry method was used to detect the protein expression change of CD68, interleukin-4(IL-4), inducible nitric oxide synthase (iNOS) and transforming growth factor-
β
1
(TGF-
β
1
).
Result
2
HE staining results showed that the inflammation of the model group was most obvious on the third day after modeling, and the disease was in the acute stage. On day 5, the inflammation was alleviated, and on day 8, the inflammation was still present but close to normal. The total saponin group and celecoxib group could improve the pathological changes of synovial tissue, and the effect of total saponin group was more obvious. Immunohistochemical results were as follows. Compared with the normal group. The expression of CD68 and iNOS in the model group increased on the 3rd,5th and 8th day of administration (
P
<
0.01). Compared with the model group, the total saponins group could reduce the expression of CD68 and iNOS (
P
<
0.05,
P
<
0.01)on the 3rd day of administration, and significantly reduced them expression on the 5th and 8th days (
P
<
0.01). Compared with the normal group, IL-4 and TGF-
β
1
expression were increased in the model group when the drug was given for three days(
P
<
0.01). Total saponin group could enhance IL-4 expression(
P
<
0.05)and decreased the TGF-
β
1
expression(
P
<
0.01). Compared with normal group, the expression of IL-4 in the model group decreased on the 5th and 8th day of administration (
P
<
0.01), and the expression of TGF-
β
1
in the model group decreased on the 5th day of administration(
P
<
0.01). Compared with the model group, the total saponins group could increase the expression of IL-4 and TGF-
β
1
at 5 d and 8 d after administration (
P
<
0.01).
Conclusion
2
Total saponins from Dioscoreae Nipponicae Rhizoma has the potential effect to treat gouty arthritis by regulating M1/M2 polarization.
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