Objective: To analyze the characteristics and possible mechanism of lipid metabolism in pregnant rats with intestinal flora imbalance. Methods: A total of 129 sexually mature female SD rats were divided into three gro...Objective: To analyze the characteristics and possible mechanism of lipid metabolism in pregnant rats with intestinal flora imbalance. Methods: A total of 129 sexually mature female SD rats were divided into three groups: non-pregnant group (untreated healthy rats), healthy pregnant group (natural insemination pregnant rats), and pregnant microflora disorder group (pregnant rats were given mixed antibiotics by gavage to build the modeling), with 43 rats in each group. The contents of TG, LDL, HDL and TC were detected by automatic biochemical analyzer, and the contents of SCD1, PGC-1 alpha, PEPCK, ApoE and MTTP genes were detected by fluorescence quantitative PCR technology. Regression analysis was used to explore the comprehensive influence of each gene on total cholesterol expression in rats. Principal component analysis was used to explore the internal mechanism of lipid metabolism in pregnant rats with intestinal flora disorder. Results: The contents of TG, TC, LDL and HDL were compared among the three groups of rats and the differences were statistically significant (P<0.05) . The expression levels of related genes (SCD1, PGC-1, PEPCK, ApoE, MTTP) in the three groups were statistically significant (P<0.05) . SCD1 content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.92±0.12) μg/mL, (1.20±0.15)μg/mL, and (1.53±0.20) μg/mL, respectively. PGC-1 alpha content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (1.34±0.21) μg/mL, (0.93±0.12) micron /mL, and (0.41±0.08) μg/mL, respectively. PEPCK content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.48±0.06) μg/mL, (0.35±0.09)μg/mL, and (0.22±0.05) μg/mL, and the differences were statistically significant (P<0.05) . Multivariate linear regression analysis showed that the influence of gene content on The effect of each gene content on TC content was in order from large to small: SCD1 (OR=4.572) , PGC-1 (OR=3.387) , PEPCK (OR=3.935) , ApoE (OR=3.597) , MTTP (OR=3.096) . The principal component analysis showed that three principal components could be extracted from five related genes of lipid metabolism in pregnant rats with intestinal dysbiosis: SCD1/PEPCK pathway (contribution rate: 36.28%) , PGC-1 /ApoE pathway (contribution rate: 30.42%) , and MTTP pathway (contribution rate: 15.37%) . Conclusion: After pregnancy, blood lipids in rats are significantly increased while the imbalance of intestinal flora will lead to decreased blood lipids. The disorder of lipid metabolism in pregnant rats with intestinal flora imbalance is mainly related to the disorder of gene expression, which further affects the functions of SCD1/PEPCK, PGC-1 /ApoE and MTTP pathways.展开更多
The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the ...The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the PI3 K/AKT signaling pathway.Here,we report that gentiopicroside(GPS),the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa,decreased lipid synthesis and increased glucose utilization in palmitic acid(PA) treated HepG2 cells.Additionally,GPS improved glycolipid metabolism in streptozotocin(STZ) treated high-fat diet(HFD)-induced diabetic mice.Our findings revealed that GPS promoted the activation of the PI3 K/AKT axis by facilitating DNA-binding protein 2(DDB2)-mediated PAQR3 ubiquitinated degradation.Moreover,results of surface plasmon resonance(SPR),microscale thermophoresis(MST) and thermal shift assay(TSA) indicated that GPS directly binds to PAQR3.Results of molecular docking and cellular thermal shift assay(CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40,Asp42,Glu69,Tyr125 and Ser129,and spatially inhibited the interaction between PAQR3 and the PI3 K catalytic subunit(P110α) to restore the PI3 K/AKT signaling pathway.In summary,our study identified GPS,which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway,as a potential drug candidate for the treatment of diabetes.展开更多
目的:通过文献研究阐述中药干预肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者代谢异常的有效性及安全性。方法:计算机检索国内外主流医药数据库中关于中医、中西医结合对比单纯西药治疗PCOS的随机对照试验(randomized con...目的:通过文献研究阐述中药干预肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者代谢异常的有效性及安全性。方法:计算机检索国内外主流医药数据库中关于中医、中西医结合对比单纯西药治疗PCOS的随机对照试验(randomized controlled trial,RCT)。参照Cochrane系统评价手册对全文的设计方案进行质量评价,采用RevMan 5.4软件进行Meta分析。结果:纳入22项RCT进行Meta分析,中药或中西药联合治疗不仅在提升排卵率这一主要研究指标上优于单纯西药治疗(P<0.05),还在改善胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、空腹胰岛素(fasting insulin,FINS)、体质量指数(body mass index,BMI)、三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)等方面优于单纯西药治疗(均P<0.05),但在调节空腹血糖(fasting blood glucose,FBG)和腰臀比(waist-to-hip ratio,WHR)方面与西药治疗差异无统计学意义(均P>0.05)。结论:中药或中西药联合干预肥胖型PCOS糖脂代谢异常,具有多途径、多靶点调控作用,无严重不良反应,优于单纯西药治疗。展开更多
目的探讨孕前体重指数(BMI)与妊娠期糖脂代谢指标的相关性及妊娠结局影响因素分析。方法选取2021年在石家庄市妇幼保健院做产前检查的孕妇103例,按照孕前BMI分为低BMI组13例、正常BMI组53例、高BMI组37例,比较3组空腹、1 h、2 h葡萄糖...目的探讨孕前体重指数(BMI)与妊娠期糖脂代谢指标的相关性及妊娠结局影响因素分析。方法选取2021年在石家庄市妇幼保健院做产前检查的孕妇103例,按照孕前BMI分为低BMI组13例、正常BMI组53例、高BMI组37例,比较3组空腹、1 h、2 h葡萄糖耐量试验(OGTT)血脂代谢指标[胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)]、妊娠不良结局发生情况,以妊娠结局为因变量,以年龄、BMI、文化程度、家庭人均月收入、既往流产史、既往妊娠史、吸烟史、饮酒、阴道大量出血、宫内大血肿为自变量,分析妊娠不良结局的影响因素。结果低BMI组、正常BMI组、高BMI组空腹OGTT、1 h OGTT、2 h OGTT、TG、TC、LDL-C水平依次升高,HDL-C水平依次降低,差异均有统计学意义(P<0.05)。高BMI组妊娠不良结局发生率显著高于正常BMI组、低BMI组(P<0.05)。103例患者共有34例发生妊娠不良结局,经多因素二元Logistic分析,BMI正常是妊娠不良结局的保护因素(P<0.05),阴道大量出血、宫内大血肿是妊娠不良结局的危险因素(P<0.05)。结论孕前BMI高会导致高血糖,高TG、TC、LDL-C,低HDL-C,导致妊娠不良结局。保持BMI正常可减少妊娠不良结局,对阴道大量出血、宫内大血肿孕妇需做好妊娠不良结局预防干预措施。展开更多
目的探讨胰岛素不同注射时机对妊娠糖尿病患者糖脂代谢、血浆D-二聚体(D-D)、抗凝血酶-Ⅲ(AT-Ⅲ)水平、妊娠结局的影响及其相关性分析。方法选取2019年10月至2022年10月赣州市妇幼保健院妇产科收治的92例妊娠糖尿病患者作为研究对象,根...目的探讨胰岛素不同注射时机对妊娠糖尿病患者糖脂代谢、血浆D-二聚体(D-D)、抗凝血酶-Ⅲ(AT-Ⅲ)水平、妊娠结局的影响及其相关性分析。方法选取2019年10月至2022年10月赣州市妇幼保健院妇产科收治的92例妊娠糖尿病患者作为研究对象,根据孕龄的不同,将患者分为早期注射组(n=52,孕龄<32周时确诊并接受胰岛素注射治疗)、晚期注射组(n=40,孕龄≥32周时确诊并接受胰岛素注射治疗),治疗4周后比较两组患者的糖脂代谢、血浆D-D、AT-Ⅲ水平及妊娠结局并进行相关性分析。结果晚期注射组患者的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)水高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组的脂代谢指标中三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组高密度脂蛋白胆固醇(HDL-C)水平低于早期注射组,差异有统计学意义(P<0.05)。晚期注射组患者的血浆D-D、AT-Ⅲ水平高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组妊娠不良结局总发生率高于早期注射组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示,2 h PG水平、HOMA-IR、FBG、HbA1c、FINS、TG、血浆D-D、AT-Ⅲ水平与胰岛素注射时机呈负相关(r=-0.723、-0.901、-0.473、-0.513、-0.804、-0.334、-0.702、-0.478,P<0.05);HDL-C、LDL-C水平与胰岛素注射时机无相关性(P>0.05)。结论妊娠早期进行胰岛素注射治疗的患者的糖脂代谢指标水平、血浆D-D、AT-Ⅲ水平低于晚期注射患者,且指标经相关性分析验证,早期注射出现不良妊娠结局的情况较少,妊娠早期注射胰岛素可以减少妊娠糖尿病患者产生的不良妊娠结局。展开更多
基金supported by the Research-Based Learning and Innovation Experimental Project for College Students in Hunan Province in 2018(Grant No.255-1097)Research-Based Learning and Innovation Experimental Project for Students in Changsha Medical University(Grant No.77-264).
文摘Objective: To analyze the characteristics and possible mechanism of lipid metabolism in pregnant rats with intestinal flora imbalance. Methods: A total of 129 sexually mature female SD rats were divided into three groups: non-pregnant group (untreated healthy rats), healthy pregnant group (natural insemination pregnant rats), and pregnant microflora disorder group (pregnant rats were given mixed antibiotics by gavage to build the modeling), with 43 rats in each group. The contents of TG, LDL, HDL and TC were detected by automatic biochemical analyzer, and the contents of SCD1, PGC-1 alpha, PEPCK, ApoE and MTTP genes were detected by fluorescence quantitative PCR technology. Regression analysis was used to explore the comprehensive influence of each gene on total cholesterol expression in rats. Principal component analysis was used to explore the internal mechanism of lipid metabolism in pregnant rats with intestinal flora disorder. Results: The contents of TG, TC, LDL and HDL were compared among the three groups of rats and the differences were statistically significant (P<0.05) . The expression levels of related genes (SCD1, PGC-1, PEPCK, ApoE, MTTP) in the three groups were statistically significant (P<0.05) . SCD1 content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.92±0.12) μg/mL, (1.20±0.15)μg/mL, and (1.53±0.20) μg/mL, respectively. PGC-1 alpha content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (1.34±0.21) μg/mL, (0.93±0.12) micron /mL, and (0.41±0.08) μg/mL, respectively. PEPCK content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.48±0.06) μg/mL, (0.35±0.09)μg/mL, and (0.22±0.05) μg/mL, and the differences were statistically significant (P<0.05) . Multivariate linear regression analysis showed that the influence of gene content on The effect of each gene content on TC content was in order from large to small: SCD1 (OR=4.572) , PGC-1 (OR=3.387) , PEPCK (OR=3.935) , ApoE (OR=3.597) , MTTP (OR=3.096) . The principal component analysis showed that three principal components could be extracted from five related genes of lipid metabolism in pregnant rats with intestinal dysbiosis: SCD1/PEPCK pathway (contribution rate: 36.28%) , PGC-1 /ApoE pathway (contribution rate: 30.42%) , and MTTP pathway (contribution rate: 15.37%) . Conclusion: After pregnancy, blood lipids in rats are significantly increased while the imbalance of intestinal flora will lead to decreased blood lipids. The disorder of lipid metabolism in pregnant rats with intestinal flora imbalance is mainly related to the disorder of gene expression, which further affects the functions of SCD1/PEPCK, PGC-1 /ApoE and MTTP pathways.
基金supported by research grants from the National Natural Science Foundation of China (No.81770816 and 81973375)the Key Project of Natural Science Foundation of Guangdong Province,China (No.2017A030311036)+1 种基金Seed Program of Guangdong Province (No.2017B090903004,China)Guangdong Provincial Key Field and Program Project (No.2020B1111100004,China)。
文摘The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes.Progestin and adipoQ receptor 3(PAQR3),a key regulator of inflammation and metabolism,can negatively regulate the PI3 K/AKT signaling pathway.Here,we report that gentiopicroside(GPS),the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa,decreased lipid synthesis and increased glucose utilization in palmitic acid(PA) treated HepG2 cells.Additionally,GPS improved glycolipid metabolism in streptozotocin(STZ) treated high-fat diet(HFD)-induced diabetic mice.Our findings revealed that GPS promoted the activation of the PI3 K/AKT axis by facilitating DNA-binding protein 2(DDB2)-mediated PAQR3 ubiquitinated degradation.Moreover,results of surface plasmon resonance(SPR),microscale thermophoresis(MST) and thermal shift assay(TSA) indicated that GPS directly binds to PAQR3.Results of molecular docking and cellular thermal shift assay(CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40,Asp42,Glu69,Tyr125 and Ser129,and spatially inhibited the interaction between PAQR3 and the PI3 K catalytic subunit(P110α) to restore the PI3 K/AKT signaling pathway.In summary,our study identified GPS,which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway,as a potential drug candidate for the treatment of diabetes.
文摘目的:通过文献研究阐述中药干预肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者代谢异常的有效性及安全性。方法:计算机检索国内外主流医药数据库中关于中医、中西医结合对比单纯西药治疗PCOS的随机对照试验(randomized controlled trial,RCT)。参照Cochrane系统评价手册对全文的设计方案进行质量评价,采用RevMan 5.4软件进行Meta分析。结果:纳入22项RCT进行Meta分析,中药或中西药联合治疗不仅在提升排卵率这一主要研究指标上优于单纯西药治疗(P<0.05),还在改善胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、空腹胰岛素(fasting insulin,FINS)、体质量指数(body mass index,BMI)、三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)等方面优于单纯西药治疗(均P<0.05),但在调节空腹血糖(fasting blood glucose,FBG)和腰臀比(waist-to-hip ratio,WHR)方面与西药治疗差异无统计学意义(均P>0.05)。结论:中药或中西药联合干预肥胖型PCOS糖脂代谢异常,具有多途径、多靶点调控作用,无严重不良反应,优于单纯西药治疗。
文摘目的探讨孕前体重指数(BMI)与妊娠期糖脂代谢指标的相关性及妊娠结局影响因素分析。方法选取2021年在石家庄市妇幼保健院做产前检查的孕妇103例,按照孕前BMI分为低BMI组13例、正常BMI组53例、高BMI组37例,比较3组空腹、1 h、2 h葡萄糖耐量试验(OGTT)血脂代谢指标[胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)]、妊娠不良结局发生情况,以妊娠结局为因变量,以年龄、BMI、文化程度、家庭人均月收入、既往流产史、既往妊娠史、吸烟史、饮酒、阴道大量出血、宫内大血肿为自变量,分析妊娠不良结局的影响因素。结果低BMI组、正常BMI组、高BMI组空腹OGTT、1 h OGTT、2 h OGTT、TG、TC、LDL-C水平依次升高,HDL-C水平依次降低,差异均有统计学意义(P<0.05)。高BMI组妊娠不良结局发生率显著高于正常BMI组、低BMI组(P<0.05)。103例患者共有34例发生妊娠不良结局,经多因素二元Logistic分析,BMI正常是妊娠不良结局的保护因素(P<0.05),阴道大量出血、宫内大血肿是妊娠不良结局的危险因素(P<0.05)。结论孕前BMI高会导致高血糖,高TG、TC、LDL-C,低HDL-C,导致妊娠不良结局。保持BMI正常可减少妊娠不良结局,对阴道大量出血、宫内大血肿孕妇需做好妊娠不良结局预防干预措施。
文摘目的探讨胰岛素不同注射时机对妊娠糖尿病患者糖脂代谢、血浆D-二聚体(D-D)、抗凝血酶-Ⅲ(AT-Ⅲ)水平、妊娠结局的影响及其相关性分析。方法选取2019年10月至2022年10月赣州市妇幼保健院妇产科收治的92例妊娠糖尿病患者作为研究对象,根据孕龄的不同,将患者分为早期注射组(n=52,孕龄<32周时确诊并接受胰岛素注射治疗)、晚期注射组(n=40,孕龄≥32周时确诊并接受胰岛素注射治疗),治疗4周后比较两组患者的糖脂代谢、血浆D-D、AT-Ⅲ水平及妊娠结局并进行相关性分析。结果晚期注射组患者的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)水高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组的脂代谢指标中三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组高密度脂蛋白胆固醇(HDL-C)水平低于早期注射组,差异有统计学意义(P<0.05)。晚期注射组患者的血浆D-D、AT-Ⅲ水平高于早期注射组,差异有统计学意义(P<0.05)。晚期注射组妊娠不良结局总发生率高于早期注射组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示,2 h PG水平、HOMA-IR、FBG、HbA1c、FINS、TG、血浆D-D、AT-Ⅲ水平与胰岛素注射时机呈负相关(r=-0.723、-0.901、-0.473、-0.513、-0.804、-0.334、-0.702、-0.478,P<0.05);HDL-C、LDL-C水平与胰岛素注射时机无相关性(P>0.05)。结论妊娠早期进行胰岛素注射治疗的患者的糖脂代谢指标水平、血浆D-D、AT-Ⅲ水平低于晚期注射患者,且指标经相关性分析验证,早期注射出现不良妊娠结局的情况较少,妊娠早期注射胰岛素可以减少妊娠糖尿病患者产生的不良妊娠结局。
