Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, ameliorates hepatic fibrosis in rats with type 2 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperglycemia may accelerate liver fibrosis. Currently, there is no effective treatment for liver fibrosis induced by type 2 diabetes. The study aim was to investigate whether RhoA/Rho kinase (ROCK) pathway is involved in liver fibrosis in the rats with type 2 diabetes and define the protective effects of fasudil on livers.</p><p><b>METHODS</b>A rat model of type 2 diabetes was established by high fat diet combined with streptozotocin (30 mg/kg, intraperitoneal injection). Animals were randomly assigned to 3 groups: control rats, untreated diabetic rats that received vehicle and fasudil-treated diabetic rats that received ROCK inhibitor fasudil hydrochloride hydrate (10 mg/kg per day, intraperitoneal injection, for 14 weeks). The morphological features of liver were observed by HE staining. Accumulation of collagen in livers was determined by Masson staining and the measurement of hydroxyproline. The mRNA expression of transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), type-I, and type-III procollagen was assessed with real-time polymerase chain reaction. The phosphorylation of myosin phosphatase target subunit-1 (MYPT1) and the protein levels of TGFβ1 and α-smooth muscle actin (a-SMA) were evaluated by Western blotting.</p><p><b>RESULTS</b>Compared with control rats, untreated diabetic rats showed higher values of collagen and hydroxyproline in livers (P < 0.01), the phosphorylation of MYPT1 and the protein levels of TGFβ1 and α-SMA were increased (P < 0.01), and the mRNA expression of TGFβ1, CTGF, type-I, and type-III procollagen was upregulated (P < 0.01); compared with untreated diabetic rats, treatment with fasudil signifcantly reduced values of collagen and hydroxyproline (P < 0.01), and decreased the phosphorylation of MYPT1 and the levels of TGFβ1 and α-SMA (P < 0.01), concomitant with the downregulation of TGFβ1/CTGF, type-I, and type-III procollagen mRNA expression (P < 0.01).</p><p><b>CONCLUSIONS</b>Fasudil ameliorates liver fibrosis in rats with type 2 diabetes at least partly by inhibiting TGFβ1/CTGF pathway and α-SMA expression. Inhibition of RhoA/ROCK may be a novel therapeutic target for liver fibrosis in diabetic non-alcoholic steatohepatitis.</p>

The relationship between serum CXC chemokine ligand-10 level and Graves' disease / 中华内分泌代谢杂志

The serum level of CXCL10 was determined in both patients with Graves' disease (GD) and normal control subjects.Serum CXCL10 levels in untreated and relapsed GD groups were higher compared with the remission group and control group( P＜0.01 ).A significant difference was observed between the former two GD groups (P＜0.01 ),but no difference was found between latter two groups( P＞0.05 ).Serum CXCL10 levels were positively correlated with FT3 and FT4,and negatively correlated with TSH by multiple linear regression analysis( P＜0.01 ).

Association between plasma visfatin and intima-media thickness of carotid artery in patients with type 2 diabetes / 中华内分泌代谢杂志

Seventy-three patients with type 2 diabetes mellitus were divided into atheroselerosis(AS) group and non-AS group according to the intima-media thickness(IMT)of the carotid artery.The plasma visfatin level in AS group was higher than that in non-As group[(44.95±10.14 vs 34.52±9.08)μg/L,P<0.05],and both of them were higher than that of the control [(24.46±7.18)μg/L,both P<0.05 ].The visfatin level Was positively correlated with IMT,waist-to-hip ratio,visceral fat thickness,fasting insulin,and HOMA insulin resistance index.Age,duration of diabetes,HbA_(1C),and visfatin level were the major risk factors for IMT of the carotid artery.