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Xueshuantong for Injection (Lyophilized, 注射用血栓通) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats

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Abstract

Objective

To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, 注射用血栓通, XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats.

Methods

Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-β1 (TGF-β1)-Smad2/3 signaling pathway were evaluated at last.

Results

There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01).

Conclusions

XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

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Authors and Affiliations

  1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Rui-lin Li, Jin-xin Wang, Hong Wang, Lu Chen & Shao-xia Wang

  2. Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Li-juan Chai, Hong Guo & Li-min Hu

  3. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Shao-xia Wang

Authors
  1. Rui-lin Li
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  2. Jin-xin Wang
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  4. Hong Guo
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  5. Hong Wang
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Contributions

Li RL analyzed the data and drafted the manuscript; Wang JX contributed in performing the experiments. Wang SX conceived and designed the experiments and revised the manuscript. Wang H and Chen L performed the HE staining test and revised the manuscript; Chai LJ and Guo H participated in the test of tight junction proteins; Hu LM supervised and coordinated all studies. All authors read the manuscript and approved the submission.

Corresponding author

Correspondence to Shao-xia Wang.

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The authors declare that they have no conflict of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81573644), Major New Drugs Innovation and Development (No. 2012ZX09101201-004), Guangxi Provincial Department of Science and Technology (No. 14125008-2-5), and Tianjin 131 Innovative Team Project and Training Program Foundation for Innovative Research Team of Higher Education in Tianjin (No. TD13-5050)

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Li, Rl., Wang, Jx., Chai, Lj. et al. Xueshuantong for Injection (Lyophilized, 注射用血栓通) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats. Chin. J. Integr. Med. 26, 825–832 (2020). https://doi.org/10.1007/s11655-020-3088-5

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  • DOI: https://doi.org/10.1007/s11655-020-3088-5

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