Objective:To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tc m-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. 99Tc m-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) and α vβ 3 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, α vβ 3, 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: 0.56-0.59, rs values: 0.49-0.69), etanercept treatment group ( r values: 0.50-0.55, rs values: 0.46-0.70) and negative control group ( r values: 0.55-0.80, rs values: 0.58-0.86, P<0.001 or P<0.05). Conclusion:Verified by 99Tc m-3PRGD 2 SPECT/CT imaging and molecular pathology, Mongolian medicine Sendeng-4 decoction can inhibit neovascularization by down-regulating vascular factors such as VEGF, resulting in delaying the progression of the disease and improving clinical symptoms.

Objective:To compare the quantitative parameters of myocardial blood flow based on SPECT imaging and those determined by PET imaging in coronary microvascular disease (CMVD) animal models, in order to clarify the accuracy and feasibility of SPECT quantitative analysis in CMVD.Methods:Seven Saanen milk goats (either male or female; (20±5) kg), were selected for establishing CMVD animal models by microsphere embolization. Dynamic myocardial perfusion imaging (DMPI) with one-day method of resting + ATP stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed before and after the modeling, respectively. One-day method of resting + ATP stress 13N-ammonia PET DMPI was performed after the modeling. The quantitative parameters determined by SPECT and PET after the modeling, including stress myocardial blood flow (SMBF), resting myocardial blood flow (RMBF) and myocardial flow reserve (MFR), were compared by paired t test. Parameters based on SPECT after modeling were compared with those of baseline levels. Bland-Altman analysis was applied to access the agreement between SPECT and PET. Results:Four of the seven experimental goats were fully imaged. The RMBF(ml·g -1·min -1; 1.52±0.27 vs 1.29±0.20), SMBF(ml·g -1·min -1; 0.74±0.19 vs 0.99±0.26), and MFR (0.53±0.16 vs 0.76±0.10) of the left ventricle (global) obtained by SPECT and PET in CMVD models were not significantly different ( t values: 3.121, 1.195, 1.930, all P>0.05). Among left anterior descending branch (LAD), left circumflex (LCX) and right coronary artery (RCA), the RMBF, SMBF and MFR values quantified by SPECT and PET were neither statistically significant ( t values: 0.182-2.734, all P>0.05). Bland-Altman analysis showed the quantitative parameters measured by SPECT and PET DMPI in left ventricle, LAD, LCX, RCA had a good consistency. The difference between the two methods for determining RMBF was up to 0.63 ml·g -1·min -1, and that of SMBF was up to 0.66 ml·g -1·min -1. All points are within the 95% confidence limit; MFR differs at most by 0.56, and 14/16 points were within 95% confidence limit. The RMBF (ml·g -1·min -1) of left ventricle measured by SPECT after modeling was not significantly different from that before modeling (1.52±0.27 vs 1.57±0.36; t=0.166, P>0.05); the SMBF (ml·g -1·min -1) and MFR after modeling were significantly lower than those before modeling (0.74±0.19 vs 2.34±0.89, 0.53±0.16 vs 1.39±0.31, t values: 3.836, 6.309, both P<0.05). Similar results were found when comparing the parameters of LAD/LCX/RCA after modeling with those before modeling (RMBF t values: 0.191, 0.235, 0.195, all P>0.05; SMBF/MFR t values: 0.411-19.911, all P<0.05). Conclusion:The blood flow quantitative parameters measured by SPECT imaging have a good consistency with those based on PET imaging, and the myocardial blood flow quantitative analysis of SPECT can evaluate the blood flow perfusion of CMVD.

目的 通过分子探针99 Tcm-3 PRGD2 SPECT在体观察药物注射于大鼠不同部位后显像剂摄取变化,探究不同注射部位对胶原诱导型类风湿性关节炎大鼠模型的影响,建立在体评估的类风湿关节炎大鼠模型评估体系.方法 取20只雌性SD大鼠(6～7周龄),随机抽样法分为实验组(A组、B组、C组)及对照组.实验组注射牛II型胶原乳剂(1.0 ml/只,1 g/L),A组注射于鼠尾根部,B组注射于背部皮下,C组注射于腹腔.1周后剂量减半,相同部位再次免疫注射.以两次皮下注射生理盐水为对照组.4周后进行视觉评估、99 Tcm-3 PRGD2 SPECT显像及病理学分析,对比统计分析.结果 CIA(胶原诱导性关节炎)组成功造模7只(A组3只,B组2只,C组2只),成模率为47％.CIA各组T/NT比值差异无统计学意义(P>0.05),与空白对照组比较有统计学意义(F=25.668,P<0.05).CIA各组关节病理滑膜细胞增生指数也明显高于空白对照组(H=9.218,P<0.05).结论 3种不同注射方式均可建立CIA大鼠模型,但背部及腹腔注射可能造成明显炎症反应,且99 Tcm-3 PRGD2有助于为CIA模型的构建提供活体可视化依据.

181 Objectives: To observe the uptake of 99mTc-3PRGD2 in rat models of rheumatoid arthritis (RA) before and after treatment with Mongolian medicine, in order to explore it`s therapeutic mechanism for RA, and provide theoretical foundation clinically. So as to establish an evaluation model to screen and verify the efficacy of Mongolian medicine in vivo. Methods: The healthy female SD rats were randomly divided into collagen-induced arthritis (CIA) group (n=176) and blank control group (n=24). Bovine collagen type II emulsion was used for arthritis induction to establish CIA models. Then the rats successfully modeled in the CIA group were randomly divided into Mongolian medicine (compound Senden-4) treatment group (n=24), TNF-α Antagonist (etanercept) treatment group (n=24) and untreated group (n=24). SPECT/CT imaging was performed before and after model established and 6 weeks after treatment. The mediastinum was select as non-target (NT) area and the target (T)/NT ratios were calculated. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and ανβ3 in each rats group before and after treatment were measured. Pathological and immunohistochemical detection were performed. Statistical methods such as one-way analysis of variance, Dunnett9s T3 method, Pearson and Spearman correlation analysis were used to analyze the data. (α = 0.05) Results: 1.There were 94 CIA models successfully established, the model success rate was about 58%, in which the clinical manifestations of the rats were significant. The pathological score injury index and the expression levels of VEGF, TNF-α, αVβ3, CD31, and CD34 in the synovial tissue were significantly different from those in the blank control group (P 0.05). After successful modeling, the difference between the two groups was statistically significant (P <0.05). 4. The T/NT value of the diseased joints in the CIA group after modeling was positively correlated with its arthritic index, serum VEGF, TNF-α, αVβ3 level, pathological score injury index and VEGF, TNF-α, αVβ3, CD31, CD34 expression levels in synovial tissues (r=0.562,0.721,0.521,0.391,0.606,0.408,0.561,0.594,0.669,0.365,P<0.05). 5. In the CIA group, the T/NT values of rats treated with etanercept and Senden-4 decreased. The T/NT values before treatment were 0.543 ± 0.223, 0.509 ± 0.140, and 0.262 ± 0.868, 0.223 ± 0.529 after treatment, respectively, and the differences were statistically significant (P <0.05). With the treatment of the two drugs, synovial neovascularization decreased, arthritis index scores and the levels of VEGF, TNF-α, αVβ3 in serum and the expression levels of VEGF, TNF-α, αVβ3, CD31, and CD34 in synovial tissues were decreased. The T/NT values of the two drug treatment groups were positively correlated with the above indicators. (Etanercept treatment group r=0.485,0.624,0.607,0.598,0.609,0.549,0.479,0.496,0.706,P<0.05; Senden-4 treatment group r=0.662,0.659,0.789,0.807,0.483,0.570,0.553,0.483,0.577,P<0.05). Conclusions: 1. Mongolian medicine compound Sendeng-4 can control the progression of rheumatoid arthritis by inhibiting angiogenesis. 2. 99mTc-3PRGD2 targeted receptor imaging has clinical application value in verifying Mongolian medicine treatment mechanism and treatment effect.

RGD肽是一种含有精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp)的三肽序列,可被整合素特异性识别,并激活传导通路,进行跨细胞膜双向信号传导,从而在细胞黏附,侵袭,增殖,存活和凋亡等过程中执行关键的调节功能.整合素在正常血管内皮细胞中几乎不表达,但在病理新生血管内皮细胞表面表达增加,利用RGD、整合素以及新生血管间的特殊关系,可广泛应用于肿瘤、类风湿性关节炎、心血管疾病、骨骼修复、抗感染等多种疾病的诊断及治疗中.本文就RGD肽目前的相关研究进展及临床应用作简要的综述.