目的:比较罗格列酮钠片与二甲双胍片分别联合胰岛素治疗2型糖尿病的疗效和安全性。方法:40例单用胰岛素控制血糖不理想的2型糖尿病患者,随机分为A组,太罗组(罗格列酮钠片)(21例);B组,二甲双胍组(19例),进行为期16周的对照观察。结果:两组治疗后空腹及餐后2小时血糖及糖化血红蛋白(HbA1c)均呈有意义的下降(Plt;0.05),从下降幅度的百分率统计,太罗组下降幅度明显高于二甲双胍组。结论:太罗联合胰岛素治疗对于血糖的控制明显优于二甲双胍联合胰岛素治疗。
Objective To evaluate the efficacy and safety of metformin for metabolic syndrome. Methods We searched The Cochrane Library, MEDLINE, EMBASE, China Biological Medicine Database, VIP, and CMAC up to the year of 2007. Handsearches and additional searches were also conducted. Randomized controlled trials of metformin for metabolic syndrome were included. Two reviewers independently extracted data from eligible studies and evaluated the quality of included studies. Meta-analysis was performed for the results of homogeneous studies by The Cochrane Collaboration’s software RevMan 4.2.9. Results Six trials involving a total of 2442 patients with metabolic syndrome were included. Meta-analysis was not performed due to the apparent heterogeneity. Metformin, compared with placebo, exhibited more favorable effects in reducing the proportion of patients with metabolic syndrome (RR 1.27, 95% CI 1.01 to 1.60), the proportion of patients with low HDL-c (RR 1.61, 95%CI 1.16 to 2.23), wide waist circumference (RR 1.64, 95%CI 1.06 to 2.55), and high FPG (RR 1.55, 95%CI 1.17 to 2.05). Metformin was also more effective in improving FPG and insulin sensitivity. The addition of metformin to atenolol plus nitrendipine was superior to atenolol plus nitrendipine alone in reducing the proportion of patients with high TG (RR 5.57, 95%CI 1.56 to 19.84), abdominal obesity (RR 14.47, 95%CI 3.34 to 62.61), and IGT (RR 16.51, 95%CI 6.06 to 45.0). Compared with low-fat diet therapy, metformin was superior in improving FPG, 2-hour postload plasma glucose, and insulin sensitivity. No differences were observed between metformin and acarbose in the reduction of TG and FPG, but metformin was less effective than acarbose in improving 2-hour postload plasma glucose. No adverse drug reactions were reported. Conclusion Metformin has beneficial effects in reducing the incidence of high FPG, IGT, and abdominal obesity. It also proved beneficial in reducing the prevalence of metabolic syndrome and increasing insulin sensitivity. The therapeutic effects of metformin on blood pressure, obesity, and lipid profile are uncertain. There is insufficient evidence to recommend the use of metformin in the treatment of metabolic syndrome due to low methodological quality, small sample size, and limited number of trials. More high quality, large-scale randomized controlled trials are required.
ObjectiveTo observe the effect of metformin on airway remodeling in asthma and its possible mechanism.MethodsTwenty-eight B/N rats were randomly divided into control group, asthma group, metformin intervention group and rapamycin intervention group. After that, the asthma model was established and intervened with metformin and rapamycin. The airway resistance and airway reactivity were measured 48 hours after the last challenge, and then the lung tissue samples were collected. Histopathological examination was used to observe airway inflammatory cell infiltration, goblet cell proliferation, airway wall fibrosis and remodeling, as well as airway smooth muscle proliferation. The expression of AMPK/mTOR pathway related proteins was detected by Western blot.ResultsCompared with the asthma group, metformin and rapamycin significantly reduced the airway responsiveness induced by high concentration of acetylcholine (P<0.05), reduced the infiltration of inflammatory cells in lung tissue and the changes of airway wall structure (P<0.05), reduced goblet cell proliferation in airway epithelium, collagen fiber deposition in lung tissue and bronchial smooth muscle hyperplasia (P<0.05). Further studies showed that the effects of metformin and rapamycin were related to AMPK/mTOR pathway. Compared with the asthma group, metformin and rapamycin could significantly reduce the expression of p-mTOR, p-p70s6k1 and SKP2, while p21 protein expression was significantly increased (P<0.05). In addition, metformin and rapamycin had similar effects (P>0.05).ConclusionMetformin can alleviate airway hyperresponsiveness and airway remodeling by activating AMPK and then inhibiting mTOR pathway, which may be a potential drug for treating asthma and preventing airway remodeling.
目的:罗格列酮(RGZ)联合二甲双胍治疗初诊2型糖尿病(T2DM)的临床疗效和安全性。方法:40例初诊2型糖尿病联用罗格列酮和二甲双胍进行12周的治疗,测定治疗前后空腹血糖(FBG)、餐后2小时血糖(PPG)、糖化血红蛋白(HbA1c)、胰岛素、C-肽、甘油三脂、体重指数(BMI),胰岛素抵抗指数(IR)、血常规、肝、肾功能等。 结果:治疗前后对照,空腹及餐后血糖、胰岛素、甘油三脂、IRI降低,具有显著差异性(Plt;0.001),体重指数变化不大(Pgt;0.05),未发生肝肾功能损害。结论:罗格列酮联合二甲双胍治疗2型糖尿病,明显改善胰岛素抵抗,降糖疗效确切。
Objective To observe the effect of metformin (Met) on inflammatory bodies and focal death in human retinal microvascular endothelial cells (hRMEC) in diabetes mellitus (DM) microenvironment. MethodsExperimental research was divided into in vivo animal experiment and in vitro cell experiment. In vivo animal experiments: 9 healthy C57BL/6J male mice were randomly divided into DM group, normal control group, and DM+Met group, with 3 mice in each group. DM group and DM+Met group mice were induced by streptozotocin to establish DM model, and DM+Met group was given Met 400 mg/ (kg · d) intervention. Eight weeks after modeling, the expression of NLRP3, cleaved-membrane perforating protein D (GSDMD) and cleaved-Caspase-1 in the retina of mice in the normal control group, DM group and DM+Met group were observed by immunohistochemical staining. In vitro cell experiments: hRMEC was divided into conventional culture cell group (N group), advanced glycation end products (AGE) group, and AGE+Met group. Joining the AGE, AGE+Met groups cells were induced by 150 μg/ml of glycation end products, and 2.0 mmol/L Met was added to the AGE+Met group. Pyroptosis was detected by flow cytometry; 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe was used to detect the expression of reactive oxygen species (ROS) in cells of each group. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to detect the relative mRNA and protein expression levels of NLRP3, cleaved-GSDMD, cleaved-Caspase-1 in each group of cells. Single factor analysis of variance was used for comparison among the three groups. ResultsIn vivo animal experiments: compared with the DM group, the expression of NLRP3, cleaved-GSDMD, and cleaved-Caspase-1 in the retina of normal control group and DM+Met group mice was significantly reduced, with significant difference among the 3 groups (F=43.478, 36.643, 24.464; P＜0.01). In vitro cell experiment and flow cytometry showed that the pyroptosis rate of AGE group was significantly higher than that of N group and AGE+Met group (F=32.598, P＜0.01). The DCFH-DA detection results showed that the intracellular ROS levels in the N group and AGE+Met group were significantly lower than those in the AGE group, with the significant difference (F=47.267, P＜0.01). The mRNA (F=51.563, 32.192, 44.473; P＜0.01) and protein levels (F=63.372, 54.463, 48.412; P＜0.01) of NLRP3, cleaved-GSDMD, and cleaved-Caspase-1 in hRMEC of the AGE+Met group were significantly reduced compared to the N group. ConclusionMet can down regulate the expression of NLRP3 inflammatory body related factors in hRMEC and inhibit pyroptosis.
目的:观察二甲双胍对慢性暴露于高糖和高游离脂肪酸的大鼠离体胰岛细胞胰岛素分泌功能的影响。方法:将大鼠离体胰岛细胞培养于5.5~16.7 mmol/L葡萄糖或5.5 mmol/L软脂酸中48 h,再加入不同浓度二甲双胍(0~5 mg/L)培养24 h。收集各组胰岛细胞,加入5.5~16.7 mmol/L葡萄糖刺激培养1 h。收集培养液,用放免法测定其基础及葡萄糖刺激的胰岛素分泌(GSIS)水平。结果:低糖组(5.5 mmol/L葡萄糖)用不同浓度二甲双胍(0~5 mg/L)处理后的β细胞基础及葡萄糖刺激的胰岛素分泌无显著性差异(Pgt;0.05);高糖(16.7 mmol/L葡萄糖)及高脂(0.5 mmol/L棕榈酸)组β细胞基础胰岛素分泌较对照组明显增高(Plt;0.01),GSIS较对照组明显降低(Plt;0.01);用2.5~5 mg/L二甲双胍干预后,高糖及高脂组β细胞基础胰岛素分泌较未治疗组明显降低(Plt;0.01),GSIS较未治疗组明显增高(Plt;0.01)。结论:低糖环境下,二甲双胍对β细胞胰岛素分泌功能无明显影响;慢性高糖及高脂可致β细胞胰岛素分泌功能受损;而2.5~5 mg/L二甲双胍能改善糖脂毒性所致β细胞胰岛素分泌功能异常。提示二甲双胍降糖效果除了其外周作用外,可能对糖脂中毒的β细胞具有直接保护作用。
Objective To explore the role of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in estrogen-induced proliferation of endometrial cancer, and explore whether metformin inhibits the proliferation of endometrial cancer cells through ERα and ERβ. Methods Stable transfected Ishikawa cells were constructed by lentivirus. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were detected by methyl thiazolyl tetrazolium assay. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell cycle were detected by flow cytometry. In addition, quantitative real-time polymerase chain reaction and Western blotting assays were used to detect changes in the expression of cyclinD1 and P21 involved in cell cycle regulation. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were observed by adding metformin to estrogen treatment. Results Down-regulation of ERα inhibited the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERα also inhibited the expression of cyclinD1 and promoted the expression of P21 (P<0.05). Down-regulation of ERα counteracted the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Down-regulation of ERβ promoted the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERβ also promoted the expression of cyclinD1 and inhibited the expression of P21 (P<0.05). Down-regulation of ERβ enhanced the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Metformin inhibited the proliferation of estrogen-induced Ishikawa cells (P<0.05), while in the down-regulated ERα Ishikawa cells or down-regulated ERβ Ishikawa cells, the inhibition of metformin on Ishikawa cells disappeared (P<0.05). Conclusions ERα may promote estrogen-induced proliferation of endometrial cancer cells, while ERβ may inhibit estrogen-induced proliferation of endometrial cancer cells. In addition, ERα and ERβ may also mediate the inhibitory effect of metformin on endometrial cancer cells.
【摘要】 目的 观察罗格列酮加二甲双胍联合治疗对2型糖尿病患者的降糖作用和安全性以及对胰岛素抵抗的影响。 方法 对2007年8月-2008年5月收治的2型糖尿病患者53例采用自身前后对照研究，48例符合入选条件的患者，接受罗格列酮加二甲双胍为期12周治疗。试验开始和结束日测定患者空腹血糖（fast plasma glucose，FPG）、血清胰岛素（serum insulin，FINS）、总胆固醇（total cholesterol，TC）、甘油三酯（triglyceride，TG）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）和糖化血红蛋白（glycosylated hemoblobin，HbA1c）以及标准餐后2 h血糖（postprandial 2 hours blood glucose，2hPPG）和胰岛素（postprandial 2 hours insulin，2hPINS）。胰岛素敏感性采用HOMA2模型公式评价。 结果 12周时FPG、FINS、2hPINS、 HbA1c均较治疗前基线时下降，分别为（8.16±2.37） mmol/L与（6.57±1.90） mmol/L，（8.84±8.07） mU/L与（7.28±6.84） mU/L，（26.87±3.13） mU/L与（20.18±13.25） mU/L，7.60%±1.71%与6.79%±1.82%，差异有统计学意义（Plt;0.05）。胰岛素抵抗指数显著低于治疗前（2.77±0.90与3.74±1.61，Plt;0.05）。其余代谢参数变化差异无统计学意义（Pgt;0.05）。 结论 罗格列酮加双胍类药物联合治疗2型糖尿病能有效降2型糖尿病患者的血糖水平，提高胰岛素敏感性，不增加体重，无低血糖发生，是一种安全有效的治疗方案。【Abstract】 Objective To observe the effect and security of rosiglitazone plus metformin in patients with type 2 diabetes mellitus, and the effect on insulin resistance. Methods Forty-eight cases suitable for this study were accepted and compared from August 2007 to May 2008. Patients accepted rosiglitazone plus metformin for 12 weeks. Fasting plasma glucose (FPG), serum insulin (FINS), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), glycosylated hemoglobin (HbA1c), postprandial 2 hours blood glucose and postprandial 2 hours insulin were determined at the first and last day of this study. HOMA 2 model formula evaluation was used in testing insulin sensitivity. Results After a 12-weeks’ treatment, FPG, FINS, 2hPINS, and HbA1c of patients were lower than those before treatment [(8.16±2.37) mmol/L vs (6.57±1.90) mmol/L; (8.84±8.07) mU/L vs (7.28±6.84) mU/L; (26.87±19.31) mU/L vs (20.18±13.25) mU/L; 7.60%±1.71% vs 6.79%±1.82%; Plt;0.05)]. Insulin resistance index was lower than that after treatment (2.77±0.90 vs 3.74±1.61, Plt;0.05). Other metabolic related parameter had no statistical difference (Pgt;0.05). Conclusion Rosiglitazone plus metformin treatment of type 2 diabetes mellitus is effective both in reducing in blood glucose levels and improving insulin sensitivity, and without gain weight, incidence of hypoglycemia. It is a safe and effective option.
ObjectiveTo observe the effect of metformin on the polarization state and photoreceptor cell activity of microglia (BV2 cells) in a high glucose environment. MethodsAn experimental study. BV2 cells were divided into a control group, a high glucose group, and a metformin+high glucose group. The cells in the high glucose group were cultured with 75 mmol/L glucose in the medium; the cells in the metformin+high glucose group were pretreated with 2 mmol/L metformin for 12 h and then placed in 75 mmo/L glucose concentration medium. The relative expression of M1 marker inducible nitric oxide synthase (iNOS), CD86 and M2 markers arginase 1 (Arg-1), and CD206 protein were detected by Western blot. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-4 were detected by enzyme-linked immunosorbent assay (ELISA). BV2 cells were co-cultured with mouse retinal photoreceptor cells (661W cells) for 24 h. The proliferation rate of 661W cells in each group was measured by methyl thiazolyl tetrazolium (MTT) colorimetric assay; the apoptosis rate of 661W cells in each group was measured by flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). An independent sample t-test was used for comparison between groups. ResultsWestern blot assay showed that the relative expression of iNOS and CD86 protein was increased and the relative expression of Arg-1 and CD206 protein was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant (t=－16.783, －11.605, 4.325, 4.649; P＜0.05); compared with the high glucose group, the relative expression of iNOS and CD86 protein was decreased and the relative expression of Arg-1 and CD206 protein was increased in BV2 cells in the metformin + high glucose group compared with the high glucose group, and the differences were all statistically significant (t=7.231, 5.560, －8.035, －8.824; P＜0.01). ELISA results showed that compared with the control group, the BV2 cells in the high glucose group had increased IL-6, TNF-α content and IL-4 content was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant (t=－64.312, －127.147, 71.547; P＜0.001); compared with the high glucose group, IL-6 and TNF-α content was significantly decreased and IL-4 content was significantly increased in BV2 cells in the metformin+high glucose group, and the differences were all statistically significant (t=44.426, 83.232, －143.115; P＜0.001). After co-culture of BV2 cells with 661W cells for 24 h, the results of MTT colorimetric assay showed that compared with the control group, the activity of 661W cells in the high glucose group was significantly reduced, and the difference was statistically significant (t=7.456, P＜0.01); compared with the high glucose group, the activity of 661W cells in the metformin+high glucose group was increased (t=－3.076, P＜0.05). TUNEL method and flow cytometry showed that the apoptosis rate of 661W cells in the high glucose group was significantly higher compared with the control group, and the differences were both statistically significant (t=－22.248, －22.628; P＜0.001); compared with the high glucose group, the apoptosis rate of 661W cells in the metformin+high glucose group was significantly decreased, and the difference was statistically significant (t=11.767, 6.906; P＜0.001, 0.01). ConclusionIn the high glucose environment, metformin inhibited the inflammatory response and attenuated the apoptosis of photoreceptor cells by regulating the polarization of microglia toward the M2 type.
Objective To systematically evaluate the efficacy and safety of letrozole combined with metformin in the treatment of polycystic ovarian syndrome (PCOS) infertility. Methods PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, and SinoMed were searched from establishment to December 31, 2022. The literature on randomized controlled trials of letrozole combined with metformin in the treatment of PCOS infertility were included. RevMan 5.4 software was used for meta-analysis. Results A total of 29 articles including 3226 subjects were included, with trial group of 1614 treated with letrozole combined with metformin, and control group of 1612 treated with letrozole alone. The meta-analysis results showed that the clinical pregnancy rate [relative risk (RR)=1.76, 95% confidence interval (CI) (1.61, 1.92)], induced ovulation rate [RR=1.22, 95%CI (1.17, 1.28)], and number of dominant follicles [mean difference (MD)=1.15, 95%CI (0.86, 1.43)] in the trial group were higher than those in the control group (P<0.05). The follicle growth time [MD=−5.41 d, 95%CI (−6.03, −4.80) d], estradiol level [MD=−7.57 pmol/L, 95%CI (−10.59, −4.56) pmol/L], luteinizing hormone level [MD=−2.27 U/L, 95%CI (−2.59, −1.95) U/L], testosterone level [MD=−1.29 nmol/L, 95%CI (−1.74, −0.85) nmol/L], fasting blood glucose level [MD=−0.91 mmol/L, 95%CI (−1.71, −0.65) mmol/L], fasting insulin level [MD=−25.93 pmol/L, 95%CI (−29.06, −22.80) pmol/L], insulin resistance index [MD=−1.40, 95%CI (−1.61, −1.19)], and the incidence of ovarian hyperstimulation syndrome [RR=0.44, 95%CI (0.22, 0.88)] in the trial group were lower than those in the control group (P<0.05). There was no statistically significant difference in follicle stimulating hormone level, incidence of adverse reactions, and spontaneous abortion rates between the two groups (P>0.05). Conclusion Existing evidence suggests that compared to using trazole alone, the combination of letrozole and metformin can improve ovulation induction and pregnancy outcomes in patients with PCOS infertility. The combination of the two drugs can reduce levels of estradiol, testosterone, and luteinizing hormone in patients, while effectively reducing the incidence of ovarian hyperstimulation syndrome.