摘要
目的通过^(99)T^(cm)-联肼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体(3PRGD_(2))显像在体观察类风湿关节炎(RA)大鼠蒙药森登-4汤治疗前后放射性分布变化,并探究其治疗机制。方法取200只雌性SD大鼠(6~7周龄),分为胶原诱导性关节炎(CIA)组(176只)和空白对照组(24只)。将CIA模型大鼠通过简单随机抽样法分为森登-4汤治疗组(24只)、依那西普治疗组(24只)和阴性对照组(24只)。造模及治疗前后均行^(99)T^(cm)-3PRGD_(2)显像,分析各组病变关节与纵隔的靶/非靶(T/NT)放射性比值,分析相应血清学、病理及免疫组织化学指标。采用单因素方差分析或Kruskal-Wallis秩和检验分析数据。相关性分析采用Pearson或Spearman相关分析。结果CIA组成功造模95只,成模率为54%(95/176)。治疗后,阴性对照组、森登-4汤治疗组、依那西普治疗组T/NT比值差异有统计学意义(0.766±0.144、0.260±0.094和0.238±0.099;F=163.00,P<0.001),而2个药物治疗组间差异无统计学意义(P>0.05)。药物治疗后,血清血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF)-α、整合素αvβ3表达水平均显著低于阴性对照组(F值:49.43~92.36,均P<0.001);关节病理滑膜细胞增生指数也明显低于阴性对照组(H=34.25,P<0.001);滑膜组织中VEGF、TNF-α、整合素αvβ3、CD31、CD34表达水平也显著低于阴性对照组(H值:13.51~26.84,均P<0.001),而2组药物治疗组间上述指标差异均无统计学意义(均P>0.05)。治疗后,森登-4汤治疗组(r值:0.56~0.59r_(s)值:0.49~0.69)、依那西普治疗组(r值:0.50~0.55r_(s)值:0.46~0.70)和阴性对照组(r值:0.55~0.80r_(s)值:0.58~0.86)的T/NT比值与上述各指标均呈正相关(P<0.001或P<0.05)。结论通过^(99)T^(cm)-3PRGD_(2)显像与分子病理验证,蒙药森登-4汤可通过下调VEGF等血管因子抑制新生血管形成,延缓病情进展、改善临床症状。
Objective To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tcm-hydrazinonicotinamide-(polyethylene glycol)4-E[(polyethylene glycol)4-c((Arg-Gly-Asp)fk)]2(3PRGD_(2))imaging.Methods A total of 200 female SD rats(age:6-7 weeks)were divided into collagen-induced arthritis(CIA)group(n=176)and blank control group(n=24).Rats in the CIA group were divided into Sendeng-4 decoction treatment group(n=24),etanercept treatment group(n=24),and negative control group(n=24)by simple random sampling method.99Tcm-3PRGD_(2)SPECT/CT imaging was performed before and after modeling and treatment.The differences of target/non-target(T/NT)ratio and serological,pathological,and immunohistochemical results among groups were compared by one-way analysis of variance or Kruskal-Wallis rank sum test.The correlation was analyzed by Pearson correlation or Spearman correlation analysis.Results There were 95(95/176)CIA models successfully established.The T/NT ratios of Sendeng-4 decoction treatment group and etanercept treatment group were lower than that of negative control group(0.260±0.094,0.238±0.099,0.766±0.144;F=163.00,P<0.001),while there was no significant difference between the two drug treatment groups(P>0.05).After drug treatment,serum levels of vascular endothelial growth factor(VEGF),tumor necrosis factor-α(TNF-α)andαvβ3 were significantly lower than those of negative control group(F values:49.43-92.36,all P<0.001),pathological score was also lower than that of negative control group(H=34.25,P<0.001),and levels of immunohistochemical makers(VEGF,TNF-α,αvβ3,CD31,CD34)were also lower than those of negative control group(H values:13.51-26.84,all P<0.001),while there were no significant differences between the two drug treatment groups(all P>0.05).The T/NT ratios were positively correlated with above indictors in Sendeng-4 decoction treatment group(r values:0.56-0.59r_(s) values:0.49-0.69),etanercept treatment group(r values:0.50-0.55r_(s) values:0.46-0.70)and negative
作者
曲宏
武瑜
张国建
王相成
王城
王焕芸
张凯秀
王文睿
王雪梅
Qu Hong;Wu Yu;Zhang Guojian;Wang Xiangcheng;Wang Cheng;Wang Huanyun;Zhang Kaixiu;Wang Wenrui;Wang Xuemei(Department of Nuclear Medicine,the Affiliated Hospital of Inner Mongolia Medical University Key Laboratory of Molecular Imaging,Inner Mongolia Autonomous Region,Hohhot 010050,China;Department of Nuclear Medicine,the Affiliated People′s Hospital of Inner Mongolia Medical University,Hohhot 010020,China;Department of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China)
出处
《中华核医学与分子影像杂志》
CAS
CSCD
北大核心
2022年第5期289-293,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
国家自然科学基金(81860311)。
