{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:48:13Z","timestamp":1784126893518,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800260"],"award-info":[{"award-number":["81800260"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetic hepatic fibrosis (DHF) is a progressive liver disease and a chronic complication of diabetes mellitus. The main cause of DHF is the activation of quiescent hepatic stellate cells (HSCs) by high glucose stimulation. Dopamine receptor D2 (DRD2)\u2010mediated dopamine signalling can be involved in the regulation of diabetic liver disease, but the exact role of DRD2 in DHF is still poorly understood. This study aimed to investigate the protective effect of DRD2 inhibition on diabetic liver fibrosis and the potential mechanism. We established both streptozotocin (STZ)\u2010induced type 1 diabetes (T1D, fed for 20\u00a0weeks) rat model and high glucose (HG, 40 mmol\/L)\u2010stimulated HSCs model. The results from both the rats with STZ and the HSCs treated with HG showed increased expression of DRD2, NOX\u20105, inflammation\u2010related proteins (IL\u20106 and TNF\u03b1) and fibrosis\u2010related proteins (TGF\u2010\u03b21, CO\u2010\u2160\/\u2162\/ IV, MMP\u20102\/9 and fibronectin). In vivo, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (T\u2010AOC) levels were significantly increased, and hematoxylin\u2010eosin (HE) staining, Masson staining, and electron microscopy revealed liver lesions and hepatocyte injury. In addition, HG\u2010treated HSCs exhibited altered oxidative stress \u2010 related indexes, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS), changed and abnormally proliferated in vitro. TGF\u2010\u03b21, the phosphorylated Smad2, nuclear NF\u03baB\u2010p65, phosphorylated NF\u03baB\u2010p65 and phosphorylated I\u03baB\u03b1 were also increased. Interestingly, haloperidol (DRD2 inhibitor) and n\u2010acetyl\u2010L\u2010cysteine (NAC, an active oxygen scavenger) reduced the above\u2010mentioned changes. In conclusion, DRD2 inhibition can reduce diabetic HSCs oxidative damage and fibrotic proliferation partly via the TGF\u2010\u03b21\/Smads and NF\u03baB pathways.<\/jats:p>","DOI":"10.1111\/1440-1681.13437","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T02:20:24Z","timestamp":1605147624000},"page":"370-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Dopamine receptor D2 inhibition alleviates diabetic hepatic stellate cells fibrosis by regulating the TGF\u2010\u03b21\/Smads and NF\u03baB pathways"],"prefix":"10.1111","volume":"48","author":[{"given":"Bingbing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoming","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases General Hospital for the Head Office of Agricultural Cultivation of Heilongjiang  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin 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