Basic Science Investigation
Preliminary study on 99Tcm-3PRGD2 imaging to verify the anti-angiogenesis mechanism and efficacy of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis
Qu Hong, Wu Yu, Zhang Guojian, Wang Xiangcheng, Wang Cheng, Wang Huanyun, Zhang Kaixiu, Wang Wenrui, Wang Xuemei
Published 2022-05-25
Cite as Chin J Nucl Med Mol Imaging, 2022, 42(5): 289-293. DOI: 10.3760/cma.j.cn321828-20201120-00421
Abstract
ObjectiveTo 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 (3PRGD2) imaging.
MethodsA 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-3PRGD2 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.
ResultsThere 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 αvβ3 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: 0.56-0.59, 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).
ConclusionVerified by 99Tcm-3PRGD2 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.
Key words:
Arthritis, rheumatoid; Neovascularization, pathologic; Radionuclide imaging; Arginine-glycine-aspartic acid; Technetium; Rats
Contributor Information
Qu Hong
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
Wu Yu
Department of Nuclear Medicine, the Affiliated People′s Hospital of Inner Mongolia Medical University, Hohhot 010020, China
Zhang Guojian
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
Wang Xiangcheng
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
Wang Cheng
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
Wang Huanyun
Department of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
Zhang Kaixiu
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
Wang Wenrui
Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University
Key Laboratory of Molecular Imaging, Inner Mongolia Autonomous Region, Hohhot 010050, China
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