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1.承德医学院,河北 承德 067000;
2.中国中医科学院 中药研究所,北京 100700;
3.中国人民解放军总医院 骨科研究所,北京 100853;
4.通化金马药业集团股份有限公司,北京 100028
王靖霞,在读硕士,从事中药药理研究,E-mail:1476162527@qq.com
*林娜,研究员,博士生导师,从事抗炎中药药理研究,E-mail:linna888@163.com
收稿日期:2018-09-04,
网络出版日期:2018-11-02,
纸质出版日期:2019-01-20
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王靖霞, 刘春芳, 何莲花, 等. 风湿祛痛胶囊对大鼠胶原诱导性关节炎的影响[J]. 中国实验方剂学杂志, 2019,25(2):89-95.
Jing-xia WANG, Chun-fang LIU, Lian-hua HE, et al. Effect of Fengshi Qutong Capsule on Collagen-induced Arthritis of Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 89-95.
王靖霞, 刘春芳, 何莲花, 等. 风湿祛痛胶囊对大鼠胶原诱导性关节炎的影响[J]. 中国实验方剂学杂志, 2019,25(2):89-95. DOI: 10.13422/j.cnki.syfjx.20190228.
Jing-xia WANG, Chun-fang LIU, Lian-hua HE, et al. Effect of Fengshi Qutong Capsule on Collagen-induced Arthritis of Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 89-95. DOI: 10.13422/j.cnki.syfjx.20190228.
目的:
2
观察风湿祛痛胶囊对大鼠胶原诱导性关节炎(CIA)的干预作用。
方法:
2
SD大鼠随机分为正常组、模型组、风湿祛痛胶囊低、中、高剂量组(0.25,0.5,1 g·kg
-1
·d
-1
),对照药甲氨蝶呤组(0.2 mg·kg
-1
·d
-1
),除正常组外,其他各组以Ⅱ型胶原和不完全弗氏佐剂免疫大鼠建立CIA模型,首次免疫后第1天给药组开始灌胃给药,每天1次,共给药19 d;首次免疫第8天开始观察大鼠关节红肿和畸形症状、评价关节炎临床积分和发病率,第19天取材后,炎症关节进行微计算机断层扫描技术检测和骨计量学分析,同时进行炎症关节组织病理学检查并从滑膜炎症、血管翳、软骨侵蚀和骨破坏等方面进行半定量评分,酶联免疫吸附测定法检测血清白细胞介素-1
β
(IL-1
β
),肿瘤坏死因子-
α
(TNF-
α
),血管内皮生长因子(VEGF),基质金属蛋白酶-3(MMP-3)和核转录因子-
κ
B受体活化因子配基(RANKL)含量。
结果:
2
风湿祛痛胶囊能剂量依赖地改善CIA大鼠炎症关节红、肿和畸形症状;与正常组比较,模型组大鼠炎症关节红、肿和畸形明显临床积分和发病率、关节滑膜炎症、血管翳、软骨侵蚀和骨破坏的病理评分显著升高(
P
<
0.01),炎症关节骨密度(BMD),骨体积分数(BV/TV),骨小梁厚度(Tb.Th),骨小梁数量(Tb.N)显著降低(
P
<
0.01),骨表面积体积比(BS/BV)和骨小梁分离度(Tb.Sp)显著升高(
P
<
0.01),血清IL-1
β
,TNF-
α
,VEGF,MMP3和RANKL的含量显著升高(
P
<
0.01);与模型组相比,各风湿祛痛胶囊组红肿、畸形症状明显改善,临床积分和发病率、关节滑膜炎症、血管翳、软骨侵蚀和骨破坏的病理评分均明显降低(
P
<
0.05,
P
<
0.01),BMD,BV/TV,Tb.Th,Tb.N明显升高(
P
<
0.05,
P
<
0.01),BS/BV和Tb.Sp明显降低(
P
<
0.05,
P
<
0.01),血清IL-1
β
,TNF-
α
,VEGF,MMP-3和RANKL的含量明显降低(
P
<
0.05,
P
<
0.01),且甲氨蝶呤组与高剂量组的作用相近。
结论:
2
风湿祛痛胶囊能有效缓解CIA的临床症状和病情,降低发病率,减轻关节的组织病理学和影像学严重度,同时抑制血清中的促炎细胞因子含量。
Objective:
2
To observe the intervention effect of Fengshi Qutong capsule on collagen-induced arthritis (CIA) in rats.
Method:
2
SD rats were randomly divided into normal group
model group
low
medium and high-dose Fengshi Qutong capsule groups (0.25
0.5
1 g·kg
-1
·d
-1
)
and methotrexate group(0.2 mg·kg
-1
·d
-1
). Except for normal group
the other groups were immunized with type Ⅱ collagen and incomplete Freund's adjuvant to establish a CIA model. On the 1
st
day after the first immunization
the administration group was given intragastric administration
once a day
for 19 days; on the 8
th
day after the first immunization
the symptoms of joint swelling and malformation of the rats were observed
and the clinical scores and incidence of arthritis were evaluated. On the 19
th
day
micro-computed tomography and bone metrology were performed
and histopathological examination of inflammatory joints was performed
andsynovial inflammation
vasospasm
cartilage erosion and bone destruction by pathological severity scores
serum interleukin-1
β
(IL-1
β
)
tumor necrosis factor-
α
(TNF-
α
)
vascular endothelial growth factor (VEGF)
matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor kappa B ligand(RANKL)were detected by enzyme linked immunosorbent assay.
Result:
2
Fengshi Qutong capsule could improve the symptoms of inflammatory joint redness
swelling and deformity in CIA rats in a dose-dependent manner. Compared with normal group
clinical score and incidence
joint synovial inflammation
vasospasm
cartilage erosion and pathological score of bone destruction in joint group were significantly increased (
P
<
0.01)
bone mineral density (BMD)
bone volume/total volume (BV/TV)
trabecular thickness (Tb.Th)
trabecularnumber (Tb.N) were significantly decreased (
P
<
0.01)
bone surface area/bone volume (BS/BV) and trabecular separation (Tb.Sp) were significantly elevated (
P
<
0.01)
and levels of IL-1
β
TNF-
α
VEGF
MMP-3 and RANKL in serum were increased (
P
<
0.01); compared with model group
clinical scores and incidence
joint synovial inflammation
vasospasm
cartilage erosion and bone destruction of each drug groupwere significantly lower (
P
<
0.05
P
<
0.01)
BMD
BV/TV
Tb.Th
Tb.N were significantly elevated (
P
<
0.05
P
<
0.01)
BS/BV and Tb.Sp were significantly decreased (
P
<
0.05
P
<
0.01)
and levels of serum IL-1
β
TNF-
α
VEGF
MMP-3 and RANKL were significantly decreased (
P
<
0.05
P
<
0.01). And the control drug methotrexate had similar effects to the high-dose group.
Conclusion:
2
Fengshi Qutong capsule can effectively alleviate the clinical symptoms and conditions of experimental rheumatoid arthritis in rats
reduce the incidence
and relieve the histopathology and imaging severity
while inhibiting the inflammatory cytokines.
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