Objective To investigate the effect of bromine domain protein 4(BRD4)inhibitor JQ1 and/or endurance exercise on glucose and lipid metabolism disorder in insulin resistant mice,and its mechanism.Methods Sixty C57BL/6 J mice were ran-domly divided into normal diet group(Con,n=10)and high fat diet group(HFD,n=50).HFD group was fed with high-fat diet for 12 weeks to establish insulin resistance model,and then randomly divided into high-fat diet group(HFD),JQ1 group(HFD+J),endurance exercise group(HFD+E)and J Q1+endurance exercise group(HFD+JE),with 10 mice in each group.The JQ1 group received intraperitoneal injection of JQ1(10 mg/kg,6 d/week,6 weeks),and the exercise group performed treadmill exer-cise(13 m/min,60 min/d,6 d/week,6 weeks).IPGTT and IPITT tests were performed after 6 weeks of intervention.Serum T-CHO,TG,HDL-C,LDL-C and NEFA were measured by microplate method.Myocardial BRD4,GLUT4,AMPK,autophagy in-dexes P62 and LC3,as well as the expressions of ER stress index GRP78,ATF4,IRE1,eIF2α and CHOP were detected by Western blotting.Results After 12 weeks of high fat feeding,body weight,fasting blood glucose and IPGTT-AUC in HFD group were significantly increased compared with Con group.After 6 weeks of intervention,serum NEFA in HFD+J group was significantly lower than that in HFD group.Serum TG,T-CHO and NEFA were significantly decreased in HFD+E group.IPITT-AUC,serum T-CHO,LDL-C and NEFA were significantly decreased,and HDL-C was significantly increased in HFD+JE group.Compared with HFD group,the expressions of p-AMPK/AMPK and GLUT4 in HFD+JE group were signifi-cantly increased.Compared with HFD group,BRD4 expression was significantly downregulated,and LAMP1 expression was significantly upregulated in HFD+J group.In HFD+E group,the expressions of BRD4 and P62 were significantly downregu-lated,and the ratio of LC3 Ⅱ/LC3 Ⅰ was significantly upregulated.The expressions of BRD4 and P62 in HFD+JE group were significantly downregulated,and the ratios of LAMP1 and LC3 Ⅱ/LC3 Ⅰ were significantly upregulated.Compared with HFD group,the expressions of GRP78,p-IRE1/IRE1 and CHOP in HFD+J group were significantly downregulated.The expressions of GRP78,p-IRE1/IRE1,p-eIF2α/eIF2α and CHOP were significantly downregulated in HFD+E group.The expressions of GRP78,p-eIF2α/eIF2α and CHOP were significantly downregulated in HFD+JE group.Conclusion JQ1 can antagonize myo-cardial BRD4 in insulin-resistant mice,improving autophagy and ERS.Yet it only contributes to a partial effect on glycolipid me-tabolism.Both endurance exercise and combined intervention can inhibit myocardial BRD4-mediated autophagy and ERS,impro-ving glucose and lipid metabolic disorder.The combination of these two interventions has a more significant effect,which may be related to BRD4 inhibition and autophagy function improvement.

Objective To investigate the effect of bromine domain protein 4(BRD4)inhibitor JQ1 and/or endurance exercise on glucose and lipid metabolism disorder in insulin resistant mice,and its mechanism.Methods Sixty C57BL/6 J mice were ran-domly divided into normal diet group(Con,n=10)and high fat diet group(HFD,n=50).HFD group was fed with high-fat diet for 12 weeks to establish insulin resistance model,and then randomly divided into high-fat diet group(HFD),JQ1 group(HFD+J),endurance exercise group(HFD+E)and J Q1+endurance exercise group(HFD+JE),with 10 mice in each group.The JQ1 group received intraperitoneal injection of JQ1(10 mg/kg,6 d/week,6 weeks),and the exercise group performed treadmill exer-cise(13 m/min,60 min/d,6 d/week,6 weeks).IPGTT and IPITT tests were performed after 6 weeks of intervention.Serum T-CHO,TG,HDL-C,LDL-C and NEFA were measured by microplate method.Myocardial BRD4,GLUT4,AMPK,autophagy in-dexes P62 and LC3,as well as the expressions of ER stress index GRP78,ATF4,IRE1,eIF2α and CHOP were detected by Western blotting.Results After 12 weeks of high fat feeding,body weight,fasting blood glucose and IPGTT-AUC in HFD group were significantly increased compared with Con group.After 6 weeks of intervention,serum NEFA in HFD+J group was significantly lower than that in HFD group.Serum TG,T-CHO and NEFA were significantly decreased in HFD+E group.IPITT-AUC,serum T-CHO,LDL-C and NEFA were significantly decreased,and HDL-C was significantly increased in HFD+JE group.Compared with HFD group,the expressions of p-AMPK/AMPK and GLUT4 in HFD+JE group were signifi-cantly increased.Compared with HFD group,BRD4 expression was significantly downregulated,and LAMP1 expression was significantly upregulated in HFD+J group.In HFD+E group,the expressions of BRD4 and P62 were significantly downregu-lated,and the ratio of LC3 Ⅱ/LC3 Ⅰ was significantly upregulated.The expressions of BRD4 and P62 in HFD+JE group were significantly downregulated,and the ratios of LAMP1 and LC3 Ⅱ/LC3 Ⅰ were significantly upregulated.Compared with HFD group,the expressions of GRP78,p-IRE1/IRE1 and CHOP in HFD+J group were significantly downregulated.The expressions of GRP78,p-IRE1/IRE1,p-eIF2α/eIF2α and CHOP were significantly downregulated in HFD+E group.The expressions of GRP78,p-eIF2α/eIF2α and CHOP were significantly downregulated in HFD+JE group.Conclusion JQ1 can antagonize myo-cardial BRD4 in insulin-resistant mice,improving autophagy and ERS.Yet it only contributes to a partial effect on glycolipid me-tabolism.Both endurance exercise and combined intervention can inhibit myocardial BRD4-mediated autophagy and ERS,impro-ving glucose and lipid metabolic disorder.The combination of these two interventions has a more significant effect,which may be related to BRD4 inhibition and autophagy function improvement.

Intermittent fasting,as a dietary nutrition program of fasting and eating alternately,mainly includes alternate-day fasting,time-restricted fasting,periodic fasting and Ramadan fasting.Positive effects of intermittent fasting on metabolic disea-ses such as obesity,diabetes and cardiovascular disease has been confirmed,but its effect on exercise performance is yet to be re-vealed.This paper summarizes the effects of intermittent fasting on anaerobic exercise,aerobic endurance exercise and strength alternation as well as related mechanism.It can provide theoretical reference for diet optimization,intermittent fasting selection and scientific exercise amony athletes,sports enthusiasts and patients with chronic diseases.

Objective:To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats.Methods:In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO 2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO 2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO 2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO 2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO 2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-β1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1β) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results:Compared with the negative control group, SiO 2 model group had a significant decrease in the body weight of rats ( P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α, IL-1β were all significantly increased ( P<0.05) . Compared with the SiO 2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly ( P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α and IL-1β were significantly decreased ( P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO 2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased ( P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased ( P<0.05) . Conclusion:Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO 2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.

Objective:To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats.Methods:In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO 2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO 2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO 2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO 2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO 2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-β1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1β) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results:Compared with the negative control group, SiO 2 model group had a significant decrease in the body weight of rats ( P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α, IL-1β were all significantly increased ( P<0.05) . Compared with the SiO 2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly ( P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α and IL-1β were significantly decreased ( P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO 2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased ( P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased ( P<0.05) . Conclusion:Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO 2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.