{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:21:37Z","timestamp":1790835697256,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T00:00:00Z","timestamp":1459382400000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Summary<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr is a newly established substrain of stroke\u2010prone spontaneously hypertensive rat (<jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>). Recently, high\u2010fat and high\u2010cholesterol (<jats:styled-content style=\"fixed-case\">HFC<\/jats:styled-content>) diet\u2010fed <jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr has been reported as a novel rat model of developing hepatic lesions similar to human non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>). The aim of this study was to investigate the detailed pathological conditions induced by <jats:styled-content style=\"fixed-case\">HFC<\/jats:styled-content> diet in <jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr rats using molecular biological methods and morphometric analysis. <jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr rats at 6\u00a0weeks of age were fed on <jats:styled-content style=\"fixed-case\">either HFC<\/jats:styled-content> diet or stroke\u2010prone (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>) diet for 2, 4, 6, 8 and 16\u00a0weeks and histopathological changes in the liver, blood chemistry and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression levels in the liver were investigated. As evidenced by the histopathological examination of the liver of the <jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr rats, hepatic steatosis and lobular inflammation were present, with gradual increasing severity from 2\u00a0weeks after the introduction of the <jats:styled-content style=\"fixed-case\">HFC<\/jats:styled-content> diet. Partial hepatic fibrosis was detected at 6\u00a0weeks and spread over the entire region of the liver with more severe bridging formation by 16\u00a0weeks. The degrees of <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010like hepatic lesions such as steatosis (the size distribution of lipid droplets), inflammation and fibrosis were quantified by morphometric analysis. Eosinophilic inclusion bodies encountered in the hepatocytes had immunoreactivity with Cox\u20104 and double\u2010membrane walls, identified as mega\u2010mitochondria. Serum <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> and bilirubins, and the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression levels related to fibrosis were closely correlated with hepatic histopathological changes. The clear feeding time\u2010dependent progression of <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2010like hepatic lesion in <jats:styled-content style=\"fixed-case\">HFC<\/jats:styled-content> diet\u2010fed <jats:styled-content style=\"fixed-case\">SHRSP<\/jats:styled-content>5\/Dmcr rats reinforced the conclusion that this strain might be a useful model of <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> and of inflammatory fibrotic liver disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iep.12169","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T17:00:44Z","timestamp":1459616444000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pathological characterization and morphometric analysis of hepatic lesions in SHRSP5\/Dmcr, an experimental non\u2010alcoholic steatohepatitis model, induced by high\u2010fat and high\u2010cholesterol diet"],"prefix":"10.1111","volume":"97","author":[{"given":"Yasushi","family":"Horai","sequence":"first","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Utsumi","sequence":"additional","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ono","sequence":"additional","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuichi","family":"Ono","sequence":"additional","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Fukunari","sequence":"additional","affiliation":[{"name":"Research Division Mitsubishi Tanabe Pharma Corporation Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2006.00465.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1309\/4UBB-BF78-F55V-50KA"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i17.2172"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01377.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00079.2013"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1946"},{"key":"e_1_2_8_8_1","first-page":"233","article-title":"Commonly used animal models of non\u2010alcoholic steatohepatitis","volume":"8","author":"Fan J.G.","year":"2009","journal-title":"Hepatobiliary Pancreat. 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