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Objective To investigate the effect of oxymatrine on liver triglyceride metabolism enzymes of apolipoprotein E(ApoE)－/－mice with fat-induced insulin resistance. Methods A total of 72 ApoE－/－mice fed with a high-fat diet for 16 weeks were randomly assigned into a model group ,an oxymatrine 25 mg/kg group ,an oxymatrine 50 mg/kg group ,and an oxymatrine 100 mg/kg group , and oxymatrine was administered p.o.for 8 weeks.C57BL/6J mice were selected to serve as the control group.Serum biochemical parameters were assessed ;Insulin resistance was assessed with the Hyper insulinemic-euglycemic clamp test ;Pathological changes in the liver were visualized by hematoxylin ( HE ) staining ;levels of gene expression of triglyceride metabolism enzymes were examined by real-time polymerase chain reaction ( PCR ) and Western-blotting. Results Administration of oxymatrine reduced body weight ,fasting blood glucose , cholesterol ,and triglyceride to varying degrees and alleviated pathological changes in the liver.Glucose infusion rates were(18.5 ± 1.6)mU · kg －1· min－1,(20.1 ± 1.8)mU · kg －1· min－1,and(21.3 ± 2.3)mU · kg －1· min－1in the oxymatrine 25 ,50 ,and 100 mg/kg groups ,respectively ,and were significantly higher than that in the model group (16.5 ± 1.6)mU · kg －1· min－1(all P ＜ 0.05) .mRNA expression levels of hormone-sensitive lipase(HSL) ,adipose triglyceride lipase(ATGL) ,and peroxisome proliferator-activated receptor γ(PPARγ)were higher in the three oxymatrine groups than in the model group ,while levels of diacylglycerol acyltransferase (DGAT1 ) were lower in the oxymatrine groups(F＝53.81 ,21.06 ,23.67 ,35.37 ;all P＜0.05) ;Levels of HSL ,ATGL ,and PPARγ were higher ,while levels of DGAT1 were lower in the oxymatrine 50 and 100 mg·kg －1groups than in the model group ( F ＝ 53.62 ,22.87 ,28.13 ,33.54 ;all P ＜ 0.05 ). Conclusions Oxidative can mitigate insulin resistance in mice fed with a high fat diet through regulating the expression of liver triglyceride metabolism enzymes.
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Objective To investigate the effects of activated protein kinase(AMPK)agonists on the expression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1a),mitofusin 2 (Mfn2) and nuclear respiratory factor1 (NRF1)in the process of lipid-induced mitochondrial dysfunction of skeletal muscles.Methods The expression of PGC1α,Mfn2 and NRF1 in C2C12 skeletal muscle cells after intervention with palmitic acid was detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting.The effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on Mfn2 and NRF1 and,the expression of Mfn2 and NRF1 in C2C12 cells induced by a PGC1α activator and PGC1α-siRNA were assessed by Western blotting.Results Palmitic acid decreased the mRNA and protein expression of PGC1α,Mfn2 and NRF1 in C2C12 cells (P＜0.05).Additionally,AICAR,rosiglitazone and metformin up-regulated PGC1α expression,regardless of the presence of palmitic acid and,AICAR reversed lipid-induced PGC1α,Mfn2 and NRF1 attenuation in C2C12 cells.Furthermore,Mfn2 and NRF1 protein expression increased with PGC1α over-expression,and decreased with down-regulated PGC1α expression.Conclusions AICAR can relieve the adverse effects of palmitic acid on PGC1α,Mfn2 and NRF1 in skeletal muscle cells.Moreover,it appears that AICAR can up-regulate Mfn2 and NRF1 expression through activating PGC1α.
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Aim To investigate the effects of Tongxin-luo capsule on oxidative stress in diabetic peripheral neuropathy (DPN )mice and its mechanisms.Meth-ods KK/Upj-Ay mice were divided into model, Tongxinluo low-dose group, Tongxinluo middle-dose group and Tongxinluo high-dose group.C57BL/6 mice were selected as control group.Mice were given drugs intragastrically for 12 weeks.Paw withdrawal latency, motor nerve conduction velocity (MNCV)were detec-ted.Activity of superoxide dismutase (SOD),gluta-thione peroxidase (GSH-Px)and content of malondial-dehyde (MDA)in blood were detected by colorimetric method.The expression of heme oxygenase-1 (HO-1 ),γ-glutamyl cysteine synthetase (γ-GCS ) of sciatic nerve was examined by real time PCR and Western blot.The protein expression of p38 MAPK,p-p38 MAPK,JNK,p-JNK,ERK,p-ERK was examined by Western blot.Results Compared with model group, paw withdrawal latency was increased and MNCV was faster in Tongxinluo group (P <0.05 ,P <0.0 1 ). SOD and GSH-Px contents significantly increased, MDA content decreased (P <0.01 ).HO-1,γ-GCS mRNA and protein expression significantly increased (P<0.05,P <0.01 )in Tongxinluo group.p-p38 MAPK protein expression decreased in Tongxinluo group (P<0.05 ).Conclusion Tongxinluo can in-hibit oxidative stress in DPN of mice via suppressing the phosphorylation of p38 MAPK.
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OBJECTIVE:To investigate the effects of Tongxinluo capsules on inflammatory cytokines of mice with diabetic pe-ripheral neuropathy. METHODS:40 KK/Upj-Ay mice were randomly divided into model group(pure water),and Tongxinluo low, medium and high dose groups [1,2 and 4 g (medicinial materials)/kg]. 10 C57BL/6 mice were selected into the control group (pure water). The drugs were given once a day for consecutive 12 weeks,ig. The pain perception threshold,motor nerve conduc-tion velocity(MNCV)and sensory nerve conduction velocity(SNCV)were detected for the mice 1 h after the last administration of drugs. The flow cytometry was used to detect the levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),cyclooxy-genase 2(COX-2)and monocyte chemoattractant protein 1(MCP-1)in serum. Real-time fluorescent quantitative polymerase chain reaction(RT-PCR)and Western blot were respectively employed to detect the mRNA and protein expressions of TNF-α,IL- 1β, COX-2 and MCP-1 in the mice’s sciatic nerves. RESULTS:Compared with control group,pain perception threshold in model group was decreased;MNCV and SNCV were slowed;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were increased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 were increased,with significant differences(P<0.01 or P<0.05). Compared with model group,pain perception threshold in Tongxinluo medium and high dose groups were increased;MNCV and SNCV were increased;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were decreased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 in sciatic nerves were decreased;the expressions of mRNA of COX-2, MCP-1 and protein of IL-1β,COX-2,MCP-1 in sciatic nerves in Tongxinluo low dose group were decreased,there were statistical significant difference(P<0.01 or P<0.05). CONCLUSIONS:Tongxinluo capsules have certain protective effects on the mice with peripheral nerve in case of diabetes by a mechanism that may be associated with the inhibition of inflammatory cytokines.