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Experimental Study Of Effect Of Effect Of Breviscapine On Oxidative Stress, Macrophage Recruitment And Expression Of Transforming Growth Factor β1 And Connective Tissue Growth Factor In Liver In Diabetic Rats

Posted on:2004-06-25Degree:MasterType:Thesis
Country:ChinaCandidate:L L XiaFull Text:PDF
GTID:2144360122999082Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Background and objective Diabetic mellitus is a serious risk for the development of renal cardiovascular, retina, and vascular disease, it is also related to liver injury. Diabetic liver injury is mainly associated with fatty changes (Fatty liver, FL) in the liver ranging from simple steatosis to steatohepatitis which may advance to cirrhosis and end-stage liver disease. The pathogenesis of diabetic liver injury consists of hepatic fat accumulation and oxidative stress with formation of free radicals. Free radicals not only directly damage liver, they also trigger formation of toxic cytokine and growth factor, and increase adhesion molecules leading an inflammatory response, tissue damage. At present, growth factor such as transforming growth factor P (TGFJ3) and connective tissue growth factor (CTGF) play critical role in the pathogenesis of liver fibrosis. A number of reports have shown that antioxidants can attenuate the complications of diabetes in patients and in experimental models including FL. Breviscapine is a compound from Chinese traditional medicine, which is from erigeron breviscapine cvant, Hand Mas and possesses a variety of pharmacological functions beyond their hemodynamic effects such as dilating micranium, reducing blood viscosity, and ameliorating microcirculation, especially as anti-oxidative stress agents. Vitamin E is a lipid-soluble chain-breaking antioxidant which protects especially biologocal membranes from lopid peroxidation. Recently, experimental study reported that vitamin E prevents elevated lipid peroxidation in liver of the streptozocin (STZ)-diabetic rats, the purpose of the present study was to compare the possible action of breviscapine and vitamin E on oxidative stress, macrophage recruitment and expression of TGFpl and CTGF in liver in diabetic rats induced by STZ. Methods Thirty two adult maleSprague-Dawley rats were separated into four groups. Control group (n=10), model group (n=10), model group treated with breviscapine (breviscapine group, n=10) and model group treated with vitamin E (vitamin E group. n=10). To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ (65mg kg-1). Breviscapine group received erigeron 20mg kg-1 d-1 by gavage, vitamin E group received vitamin E 20mg kg-1 d-1 by gavage. 8 weeks after STZ injection, the following determinations were done in samples: (1) plasma glucose (BG), serum lipid including total cholesterol (TC), triglyceridel (TG) were determined according to standard methods; (2) liver tissue malondiadehyde (MDA), superoxide diamutase (SOD), catalase (CAT), GSH, glutathione peroxidase (GSH-Px), glutathione-S-transferase (GSH-ST) were determined by spectrophotometric method. Liver lesions were evaluated using hematoxylin-eosin (HE) and Masson staining. Liver fatty changes were evaluated with oil red O staining. Immunohistochemistry for EDI (monocytes/ macrophages), TGFJ31 and CTGF were performed by streptavidin-biotin comblex (SABC) technique. Liver fatty changes, fibrosis and TGFpl and CTGF immunohistochemistry were assessed on 10 consecutive microscopic fields per section, exammined at a magnification of x 100. Liver fatty, fibrosis and amount of EDI. TGFpM and CTGF was graded according to the following scale: 0=absent; l=mild (involving10% per microscopic field ); 2=moderate (>11 and 25%); 3=severe (>26 and 50%) or 4=very severe (>50%). Results 1. Body weight (BW), BG, TC and TG levels: 8 weeks after STZ injection, BW was significantly decreased in diabetic rats, breviscapine could not prevented the decline in BW. vitamin E could significantly ameliorate the decline in BW. There was a significant increase in fasting BG in diabetic rats compared with control group, although the BG levels of breviscapine group were lower than those in the diabetic group, there was no statistically significant difference. On the other hand, BG levels of vitamin E were lower than diabetic group. Compared with control group, diabetic rats developed elevated plasma TG, TC levels,adminstration of breviscapine c...
Keywords/Search Tags:Diabetes, Live, Fat accumulation, Oxidative stress, Macrophages, Transforming growth factor β1, Connective growth factor, Breviscapine, Vitamin E
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