title: Protection of tauroursodeoxycholic acid on high glucose-induced human retinal microvascular endothelial cells dysfunction and streptozotocin-induced diabetic retinopathy rats.
abstract: BACKGROUND
  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.
  
  
  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 (30mg/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 (5.0μM, 25.0μM and 125.0μM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China.
authors.forename: Chun-Fei
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Yuan
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qin
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Jun-Fei
authors.initials: JF
authors.lastname: Gu
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Zhao
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Hou
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Jiangsu Integrative Hospital of Chinese Traditional and Western Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Wei-Quan
authors.initials: WQ
authors.lastname: Bu
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jumpcan Pharmaceutical Co., Ltd, Taixing 225400, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Jumpcan Pharmaceutical Co., Ltd, Taixing 225400, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Jumpcan Pharmaceutical Co., Ltd, Taixing 225400, PR China.
authors.forename: Zi-Bo
authors.initials: ZB
authors.lastname: Dong
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: wenmoxiushi@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: jxiaobin2005@hotmail.com.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Jia
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D042783:Endothelial Cells / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000166:cytology*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D019001:Nitric Oxide Synthase; D005947:Glucose
keywords: Calcium Dobesilate (PubChem CID: 29963); Diabetic retinopathy; HRMECs; Streptozotocin (PubChem CID: 5300); Tauroursodeoxycholic acid; Tauroursodeoxycholic acid (PubChem CID: 9848818); Ursodeoxycholic acid (PubChem CID: 31401)