title: Long-term administration of fasudil improves cardiomyopathy in streptozotocin-induced diabetic rats.
abstract: Inhibition of Rho kinase (ROCK) has been shown to improve diabetic-related disorders. In this study, the cardio-protective effects and potential mechanisms of fasudil, a selective ROCK inhibitor, on diabetic cardiomyopathy were investigated in a streptozotocin (STZ)-induced diabetic rat model. Eight weeks after diabetes was induced by a single tail vein injection of 60 mg/kg STZ, rats were administered long-term fasudil or captopril as a control over a four-week period. Similar to the effect of captopril, fasudil treatment significantly protected against STZ-induced hemodynamic, histopathologic changes and decreased serum lactate dehydrogenase and creatine phosphokinase. Moreover, fasudil significantly down-regulated ROCK I mRNA expression and ROCK activity, reduced cardiac collagen deposition, and decreased the incidence of apoptosis and ratio of Bax/Bcl-2 protein expression. Additionally, fasudil potently elevated superoxide dismutase activity and suppressed the extent of lipid peroxidation in sera and hearts of diabetic rats. Our findings indicated that long-term treatment with fasudil could improve cardiac dysfunction, attenuate myocardial injury and prevent pathological changes in a rat model of diabetic cardiomyopathy. These effects could be attributed to regulation of antioxidative activities, suppression of myocardial hypertrophy, apoptosis, fibrosis and subsequent cardiac remodeling. These results may help to expand the clinical application of fasudil for diabetic cardiomyopathy.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Hebei Medical University, 326, Xinshi South Road, Shijiazhuang 050091, Hebei, China.
authors.forename: Sheng-jiang
authors.initials: SJ
authors.lastname: Guan
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Ma
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: J Woodrow
authors.initials: JW
authors.lastname: Weiss
authors.forename: Qian-yu
authors.initials: QY
authors.lastname: Guo
authors.forename: Jiang-yan
authors.initials: JY
authors.lastname: Wang
authors.forename: En-sheng
authors.initials: ES
authors.lastname: Ji
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002216:Captopril; D013482:Superoxide Dismutase; D054460:rho-Associated Kinases; C049347:fasudil