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ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
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Objective To observe the changes of serum ferritin and 25-(OH) vitamin D3 in patients with diabetic cranial neuropathy.Methods There were 50 patients without diabetic Cranial neuropathy,46 patients with diabetic cranial neuropathy,and 40 cases of normal control group.The changes of serum ferritin and 25-hydroxy vitamin D3 were observed in each group.The correlation between two indexes and the correlation with diabetic cranial neuropathy were analzyzed.Results The serum ferritin levels in diabetic group and diabetic neuropathy group were significantly higher than those in normal control group (P ＜ 0.01),and its level in patients with diabetic cranial neuropathy [(687.54 ± 65.38)ng/ml] was significantly higher than that of patients without diabetic cranial neuropathy [(497.28 ± 46.39) ng/ml,P ＜0.01].The serum 25-(OH) vitamin D3 levels in the diabetic group and diabetic neuropathy group were lower than those in the control group (P ＜ 0.01),and its level in patients with diabetic cranial neuropathy [(26.45 ± 8.93)nmol/l] was significantly less than that of patients without diabetic cranial neuropathy [(37.19-± 9.74)nmol/L,P ＜ 0.01].Serum ferritin levels were positively correlated with 25-(OH) vitamin D3 (r =-0.59,P ＜ 0.01).Multivariate unconditional Logistic regression analysis showed that diabetic neuropathy was negatively correlated with 25-(OH) vitamin D3 (P ＜ 0.05).Conclusions The increases of serum ferritin and 25-(OH) vitamin D3 are closely related to the occurrence and development of diabetic cranial neuropathy,which provides the theoretical basis for clinical intervention therapy.
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Objective To investigate the changes of serum ferritin and homocysteine of diabetic patients,to explore its correlation with diabetic gastroparesis.Methods Pure 50 patients with diabetes,50 patients with diabetic gastroparesis,and 50 cases of normal control group were chosen.The serum ferritin levels were measured with chemiluminescence method,the serum homocysteine levels were measured with enzyme linked immunosorbent assay (ELISA) method.The changes of serum ferritin and serum homocysteine in each groups were observed.Its relationship with diabetic gastroparesis was studied.Results For all diabetic patients,the serum ferritin and homocysteine levels were significantly higher than those in normal control group (P ＜ 0.01).Patients with diabetic gastroparesis was higher than those of pure diabetes (P ＜ 0.01).Serum ferritin levels was positively correlated with glycosylated hemoglobin and homocysteine (r =0.62,0.78,P ＜ 0.01).Multi-factor analysis showed that serum ferritin,and homocysteine level was positively associated with diabetic gastroparesis (P ＜ 0.05).Conclusions The increases of serum ferritin and homocysteine levels were closely related to the occurrence and development of diabetic gastroparesis.They can be used as one of parameters of diabetic gastroparesis,and provide theoretical basis for clinical intervention therapy.
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Objective To investigate the relationship between serum levels of homocysteine (HCy) and adiponectin (APN) in patients with type 2 diabetes mellitus(T2DM).Methods 65 patients with T2DM (diabetes mellitus group) and 25 healthy controls (control group) matched in the age and sex were recruited in the study.Serum HCy,APN,fasting plasma glucose (FPG),fasting insulin (FINS),total cholesterol (TC) and triglyceride (TG) were simultaneously measured.The homeostatic model assessment for insulin resistance(HOMA-IR) was calculated according to FPG and FINS.All the serum indicators were compared between the two groups.Results Serum level of HCy in T2DM group was (15.74 ± 2.76) μmol/L,which was significantly higher than (6.98 ± 1.94) μmol/L in the healthy control group (t =16.88,P ＜ 0.01).The serum level of APN in T2DM group was (8.14 ± 2.70) mg/L,which was significantly lower than (16.10 ± 1.93)mg/L in the healthy control group (t =13.44,P ＜ 0.01).Serum levels of FPG,HOMA-IR,TC,TG in T2DM group were significantly higher than those in the healthy control group (t =10.62,17.49,6.30,7.52,P ＜ 0.05).Serum level of APN in HCy ≥ 15μmol/L group was significantly decreased compared with HCy ＜ 15μmol/L group.Serum level of HCy was negatively correlated with APN in T2DM group after the influence of FPG,HOMA-IR,TG,TC were corrected in the partial correlation analysis.Conclusion In T2DM group,serum level of HCy was increased,but serum level of APN was decreased,serum HCy was negatively correlated with APN,higher serum level of HCy and lower serum level of APN are related with the process of insulin resistance and T2DM.
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Objective To investigate the changes of serum homocysteine and it s relationship with oxidative stress and diabetic microangiopathy.Methods Eighty health participants were recruited as control 100 type 2 diabetis patients without diabetic microangiopathy were recruited as DM group,100 type 2 diabetis patients with diabetic nephropathy were recruited as DN group,and 100 type 2 diabetis patients with diabetic retinopathy were recruited as DR group.Their serum levels of homocysteine,malonaldehyde(MDA),superoxide dismutase (SOD)and glutathione(GSH)were measured.Results The homocysteine was(98.86 ± 21.46),(198.95 ±19.35),(138.65 ± 15.25)ng/L in the DM,DN and DR group respectively,which were signigicantly higher than that of(62.48 ± 15.36)ng/L in the control group(F =7.95,P ＜ 0.01).MDA was(17.49 ± 1.64),(22.47 ± 1.86)and(22.47 ± 1.86)mmol/L,which was significantly higher than that of(11.86 ± 0.48)mmol/L in the control group(F =6.89,P ＜0.01).The homocysteine and MDA in the DN and DR group were both significantly higher than those in the DM group(P ＜ 0.01).The SOD and GSH was(107.80 ± 15.62)mg/L and(179.26 ± 25.8)mg/L in the DM group,(79.86 ± 14.63)mg/L and(143.36 ± 21.75)mg/L in the DN group,(89.34 ± 12.75)mg/L and(156.96 ± 19.35)mg/L in the DR group,which were significantly higher than those of(128.32 ± 19.21)mg/L and(237.38 ± 27.31)mg/L in the control group(F =7.89 and 8.76 respectively,P＜0.01).The SOD and GSH in the DN and DR group were both significantly lower than those in the DM group(P ＜ 0.01),and the DN group was significantly lower than the DR group(P ＜ 0.01)Serum homocysteine was positively correlated with MDA(r =0.79,P ＜ 0.05),and negtively correlated with SOD and GSH(r =-0.71 and-0.78,P ＜0.01).Conclusion Diabetic microangiopathy patients have higher serum homocysteine level and severe oxidative stress.Oxidative stress were related to higher serum homocysteine level.The higher serum homocysteine level and oxidative stress might play an important role in development of diabetic Microangiopathy
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Objective To study the changes of endothelin,nitric oxide and vascular endothelial growth factor level in patients with type 2 diabetic retinopathy (DR). Methods Eighty diabetes patients (53 with diabetic retinopathy and 27 without). Another 30 healthy volunteers were recruited as control. Plasma ET and VEGF levels were measured by enzyme-linked immunosorbent assay. NO levels were measured by nitrate reductase method. Results Plasma levels of ET were higher in patients with type 2 diabetes with DR (DR)(80. 68 ± 13.57) mg/L than (65. 33 ± 11.24) mg/L, (45.25 ±9. 06) mg/L, in control and in type 2 diabetes patients without DR (NDR) (Ps ＜ 0, 01 ). Plasna levels of NO in DR group (69. 82 ± 14. 89) μmol/L were higher than (37. 85 ±-9. 11 ) μmol'L, in control group,but lower than (77.52 ±± 18.56) μmol/L in NDR group (Ps ＜ 0. 05 ). Plasma levels of VEGF ( 110. 52 ± 25.65 ) μg/L in DR were significantly increased compared with control (82.42 ± 18. 47 ) μg/L, and NDR(97.55 ±25.61)μg/L, (Ps ＜0.05).Conclusion ET, NO and VEGF may be involved in the pathogenesis of type 2 diabetic retinopathy.