Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats

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• 作者：Chun-fei Wang^a ; ^b ; ¹ ; Jia-rui Yuan^a ; ¹ ; Dong Qin^a ; ¹ ; Jun-fei Gu^a ; Bing-jie Zhao^a ; Li Zhang^a ; Di Zhao^a ; Juan Chen^a ; Xue-feng Hou^a ; ^b ; Nan Yang^a ; Wei-quan Bu^c ; Jing Wang^a ; Chao Li^d ; Gang Tian^d ; Zi-bo Dong^d ; Liang Feng^a ; ^b ; ^⁎ ; ^{wenmoxiushi@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xiao-bin Jia^a ; ^b ; ^{jxiaobin2005@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TUDCA ; Tauroursodeoxycholic Acid ; HRMECs ; Human Retinal Microvascular Endothelial Cells ; STZ ; Streptozotocin ; DR ; Diabetic Retinopathy ; DM ; Diabetes Mellitus ; UDCA ; Ursodeoxycholic Acid ; CDDT ; Calcium Dobesilate Dispersible Tablets ; HE ; Hematoxylin and Eosin ; NO ; Nitric Oxide ; ICAM-1 ; Intercellular Adhesion Molecule-1 ; NOS ; Nitric Oxide Synthase ; NF-κB p65 ; Nuclear Factor κB p65 ; VEGF ; Vascular Endothelial Growth Factor ; OD ; Optical Density ; SD ; Standard Deviation ; PBS ; Phosphate Buffer Saline
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：5 June 2016
• 年：2016
• 卷：185
• 期：Complete
• 页码：162-170
• 全文大小：8389 K

文摘

Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold “Clearing heat and detoxification, Removing liver fire for improving eyesight” functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored.

Materials and methods

The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats’ model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30 mg/kg). The cell supernatant and rats’ serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs.

Results

After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0 μM, 25.0 μM and 125.0 μM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500 mg/kg/d and 250 mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA.

Conclusion

The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.