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41.
目的研究甲氰咪胍对金属蛋白酶组织抑制因子(TIMP)、基质金属蛋白酶(MMP)等纤维化相关指标的作用,探讨甲氰咪胍对NASH大鼠肝纤维化进展的影响。方法26只雄性SD大鼠随机分为正常饮食对照组(n=6)、高脂饮食模型组(n=10)和甲氰咪胍治疗组(n=10),实验时间12周。生化法检测血清AST、ALT、ALP、TBIL、肝组织1℃,放免法检测HA,RT-PCR法检测TIMP-1、TIMP-2、MMP2、MMP13 mRNA的表达。病理切片检查和Ⅰ型胶原免疫组化染色观察组织学改变。结果与模型组比较,治疗组大鼠肝功改善,HA水平下降,TIMP-1、TIMP-2、MMP2表达降低,但仍高于对照组,与模型组无显著差异,MMP13表达无降低。治疗组肝组织脂肪变改善,炎症减轻,Ⅰ型胶原沉积减少。结论甲氰咪胍具有一定抗纤维化的作用。 相似文献
42.
Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease 总被引:5,自引:0,他引:5
Sakugawa H Nakayoshi T Kobashigawa K Yamashiro T Maeshiro T Miyagi S Shiroma J Toyama A Nakayoshi T Kinjo F Saito A 《World journal of gastroenterology : WJG》2005,11(2):255-259
AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease. However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type VI collagen 7S domain and hyaluronic acid. METHODS: One hundred and twelve patients with histologically proven NAFLD were studied. RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type VI collagen 75 domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type VI collagen 7S domain, 86% and hyaluronic acid, 92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type VI collagen 7S domain (≥5.0 ng/mL), 84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis. CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis. 相似文献
43.
Kumar D Farrell GC Kench J George J 《Journal of gastroenterology and hepatology》2005,20(9):1395-1400
BACKGROUND AND AIM: Obesity associated hepatic steatosis has been suggested to have a premalignant potential. We determined whether hepatic steatosis predisposes to liver cancer in persons with chronic hepatitis C virus (HCV) infection. METHODS: We compared the histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed hepatocellular carcinoma (HCC) with matched controls who did not. Cases were aged (mean) 54.7 years, 84% males, 76% genotype 1, and 64% fibrosis stage 4; and controls were matched for these characteristics. Those with a sustained virologic response to antiviral therapy were excluded. RESULTS: Duration of HCV infection, concomitant alcohol intake, body mass index and indices of past hepatitis B virus (HBV) infection were comparable between the groups. Controls were followed for a longer period after the index liver biopsy than were cases (113 months vs 55 months, P < 0.001). As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded by semiquantitative histological assessment, steatosis was comparable among cases and controls. The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC. CONCLUSIONS: Hepatic steatosis does not augment the risk of hepatocarcinogenesis in patients with chronic HCV infection. 相似文献
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45.
随着生活水平的提高和生活方式的改变,糖尿病合并非酒精性脂肪性肝病(NAFLD)的发病率不断升高.虽有多种方法治疗糖尿病合并NAFLD,如生活方式的改变、增加胰岛素敏感性、抗氧化、调节血脂紊乱以及对一些风险因素的防治等,但由于其病因和发病机制尚未完全明了,仍缺乏更为有效的治疗方法.本文就近年来对糖尿病合并NAFLD的治疗进展作一综述. 相似文献
46.
Hussein O Szvalb S Van den Akker-Berman LM Assy N 《Digestive diseases and sciences》2002,47(9):1926-1931
Fatty infiltration is associated with an increased incidence of complications and mortality after liver resection and transplantation. The aim of this study was to document the regenerative response in patients with hepatic steatosis and mild inflammatory activity (NASH) and to identify potential levels of impaired regeneration. Ki-67 immunostaining was similar in patients with NASH (ages 44.6 ± 15 years, labeling index, 0.4 ± 0.3%) when compared to patients with chronic hepatitis C infection (ages 50.7 ± 17 years, labeling index; 0.4 ± 0.7%). The labeling index was not increased in patients with a higher level of inflammation, a higher level of fibrosis, and a higher level of fat in either study group. In conclusion, liver regeneration is not altered in patients with nonalcoholic steatohepatitis, suggesting that the delayed postoperative liver failure seen in these patients may be related to another mechanism. 相似文献
47.
48.
Yongming Pan Yili Rong Junjie Huang Keyan Zhu Jiaojiao Chen Chen Yu Minli Chen 《Journal of diabetes and its complications》2019,33(4):278-288
Aims
A long-term high-fat/cholesterol (HFC) diet leads to hepatic insulin resistance (IR), which is associated with autonomic dysfunction and cardiovascular diseases risk increasing. However, whether this occurs in Tibetan minipigs remains unknown. We tested that a long-term HFC diet caused hepatic IR and promote cardiovascular disorders in Tibetan minipigs, and are associated with the reduction of cardiovagal tone and baroreflex sensitivity (BRS).Methods
Male Tibetan minipigs were fed either a standard diet or a HFC diet, and were euthanized at 12?weeks. Thereafter, the minipigs were tested for biochemical blood indices, glucose tolerance, blood pressure, heart rate variability (HRV), BRS, and insulin receptor substrate (IRS)-associated gene and protein expression levels, as well as cardiac function.Results
HFC-fed minipigs developed IR by increasing body weight, total cholesterol, fasting blood glucose and insulin levels, and nonesterified fatty acid (NEFA) and high sensitive C-reactive protein (hs-CRP) levels, glucose intolerance. Increased adipose cell size, hepatic fat deposition, malondialdehyde (MDA) content and NEFA level, down-regulation of IRS1, IRS2, PI3K, Akt, p-Akt, Glut2 and PGC1ɑ expression concomitant with up-regulation of mTOR, GSK3β, TNF-ɑ, FOXO1, p-mTOR and p-p70S6K expression in the liver tissue, as well as hypertension and left ventricular diastolic dysfunction were observed in HFC-fed minipigs. HRV parameters and BRS values were further significantly reduced. Furthermore, multiple linear regression analysis showed that the development of hepatic IR toward cardiovascular disease was associated with low HFnu, RMSSD, BRS and LV ?dp/dtmax, high NEFA, high hepatic TG content.Conclusion
These data suggest that HFC-fed Tibetan minipigs develop hepatic IR and promote cardiovascular disorders, and are associated with lower cardiovagal tone and BRS. 相似文献49.
Saumya Jayakumar Michael S. Middleton Eric J. Lawitz Parvez S. Mantry Stephen H. Caldwell Hays Arnold Anna Mae Diehl Reem Ghalib Magdy Elkhashab Manal F. Abdelmalek Kris V. Kowdley C. Stephen Djedjos Ren Xu Ling Han G. Mani Subramanian Robert P. Myers Zachary D. Goodman Nezam H. Afdhal Rohit Loomba 《Journal of hepatology》2019,70(1):133-141
50.