Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

Linagliptin alleviates fatty liver disease in diabetic db/db mice

AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) was assessed by immunohistochemistry. RESULTS In 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independent to changes in the plasma glucose levels. CONCLUSION The DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice.

linagliptin与靶标DPP4作用机理及分子设计研究

采用分子对接方法对目前刚刚上市的糖尿病抑制剂linagliptin与其靶标DDP4进行研究,建立了合理、有效的对接模型,获得了其活性口袋周围的环境分布情况。并根据这些结论进行了分子设计,对理论设计的新分子通过已建立的模型进行预测,其结果显示它具有比linagliptin更好的对接结合能。该研究结果可为实验工作者合成新药提供理论参考。

The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review

BACKGROUND Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride(a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin.Gliclazide(another newer sulfonylureas) has shown similar glycemic efficacy and 50% decreased risk of hypoglycemia compared to glimepiride.AIM Considering the absence of cardiovascular outcome trials for gliclazide, we decided to conduct a systematic review of the literature to assess the cardiovascular(CV) safety by assessing the risk for major adverse CV events and hypoglycemia risk of gliclazide vs linagliptin in patients with type 2 diabetes(T2D).METHODS This systematic review followed the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to analyze all the clinical studies published from 2008 that compared the two drugs in patients with T2D with no risk of CV disease(CVD). We included only evidence designated high quality by the Oxford Center for Evidence-based Medicine-Levels of Evidence.RESULTS Eight clinical studies were included in the narrative descriptive analysis(gliclazide: 5 and linagliptin: 3). The CV safety of gliclazide in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial and of linagliptin in the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin(CARMELINA) and CARdiovascular Outcome study of LINAgliptin vs glimepiride in patients with T2D(CAROLINA)trials were excluded from the comparative analysis as these trials demonstrated CV and hypoglycemia benefits in patients at high risk of CVD. However, since these are landmark trials,they were discussed in brief to show the CV benefits and low hypoglycemia risk of gliclazide and linagliptin. We did not find any study comparing gliclazide with linagliptin. Hence, direct comparison of their major adverse CV events and hypoglycemia risk could not be carried out.However, the literature meeting the inclusion criteria showed that both drugs were effective in achieving the desired glycemic control and had low major adverse CV events and hypoglycemia risk in adult patients with no history of CVD.CONCLUSION Gliclazide can be considered an effective and safe glucose-lowering drug in T2D patients with no established CVD but at high risk of CVD due to their T2D status. Future randomized controlled trials comparing gliclazide with linagliptin or dipeptidyl peptidase-4 inhibitors can confirm these findings.

Efficacy of anagliptin as compared to linagliptin on metabolic parameters over 2 years of drug consumption: A retrospective cohort study

AIM To evaluate the comparative effectiveness of anagliptin and linagliptin on the clinical parameters in patients with type 2 diabetes mellitus(T2 DM). METHODS A 2-year retrospective cohort study was conducted in patients with T2 DM who received anagliptin and linagliptin. We enrolled 234 patients(anagliptin group, 117 patients; linagliptin group, 117 patients). RESULTS The glycemic control considerably improved 3, 6, 12, and 24 mo after the administration of both dipeptidyl peptidase-4(DPP-4) inhibitors. Following the administration of anagliptin, the diastolic blood pressure and serum total cholesterol levels decreased. However, serum high-density lipoprotein cholesterol levels increased and urinary albumin-creatinine ratio decreased following linagliptin administration. Furthermore, the liver function improved after the administration of linagliptin.CONCLUSION These findings suggest that that the efficacy of DPP-4 inhibitors on the blood pressure, lipid profile, and liver function differs between anagliptin and linagliptin.

Effect of Llinagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy

Objective:To explore the effect of Linagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy.Methods: A total of 98 patients with diabetic nephropathy admitted to the Hospital from January 2017 to September 2018 were enrolled. The patients were divided into two groups according to the random double-blind method, with 49 cases in each group. The control group was treated with Metformin, whereas the experimental group was treated with Linagliptin plus Metformin. After 3 months of continuous treatment, the renal function [urinary albumin excretion rate, 24 h urine protein quantitation and serum creatinine], glycolipids metabolic levels [glycated hemoglobin, fasting blood glucose, total cholesterol and triglycerides], monocyte chemoattractant protein-1, tumor necrosis factor receptor, high-sensitivity C-reactive protein, and adverse reactions were compared between the two groups.Results:After 3 months of treatment, the levels of UAER, 24 h Upor and Scr in the experimental group were shown to be lower than those in the control group, and the difference was statistically significant. After 3 months of treatment, the levels of HbA1c, FPG, TC and TG in the experimental group were shown to be lower than the control group, and the difference was statistically significant. After 3 months of treatment, the levels of MCP-1, sTNFR1 and hs-CRP in the experimental group were lower than those in the control group, and the difference was statistically significant. There was no significant difference in incidence of adverse reactions between the two groups.Conclusion: For patients with diabetic nephropathy, Linagliptin is with higher safety, which can help improve their glycolipids metabolic levels and renal function, reduce the inflammatory response and the levels of MCP-1 and sTNFR1, and yet incur fewer adverse reactions.

利格列汀联合司美格鲁肽治疗2型糖尿病的效果观察

目的观察利格列汀联合司美格鲁肽治疗2型糖尿病(T2DM)的效果。方法将2020年3月至2023年2月我院收治的100例T2DM患者分为两组。对照组采用利格列汀治疗,观察组采用利格列汀联合司美格鲁肽治疗。比较两组的治疗效果、血糖水平及不良反应。结果观察组治疗总有效率高于对照组(P<0.05)。治疗后,观察组的FPG、2hPG低于对照组,FC-P、2hC-P高于对照组(P<0.05)。两组的不良反应发生率比较无统计学差异(P>0.05)。结论利格列汀联合司美格鲁肽治疗T2DM的效果较好,可维持患者血糖水平稳定,调节胰岛功能。

利格列汀调控巨噬细胞极化和破骨细胞形成缓解磨损颗粒诱导的骨质溶解

背景:研究发现,在利格列汀的干预下,巨噬细胞更多的由M1转向M2极化,降低了相关炎性因子的释放,缓解了局部炎症。目的:探讨利格列汀对巨噬细胞极化、破骨细胞活化及磨损颗粒诱导炎性骨溶解的影响。方法:(1)细胞实验:①巨噬细胞极化:将RAW264.7细胞分4组培养,对照组细胞加入高糖培养基;M1诱导组加入M1诱导培养基(含脂多糖100 ng/mL和干扰素γ20 ng/mL的高糖培养基)模拟炎症环境;利格列汀低、高剂量组分别加入50,200 nmol/L利格列汀处理4 h后加入M1诱导培养基。巨噬细胞极化诱导24 h后,分别进行巨噬细胞极化免疫荧光染色和RT-PCR检测。②破骨细胞活化:将RAW264.7细胞分为4组培养,对照组使用高糖培养基培养,破骨细胞诱导组、利格列汀低剂量组及高剂量组进行破骨细胞诱导,待微小破骨细胞成形后,用利格列汀(50,200 nmol/L)分别干预细胞3 d,进行细胞抗酒石酸酸性磷酸酶染色和RT-PCR检测。(2)动物实验:将24只雄性C57BL/6J小鼠随机分为4组,即假手术组、模型组、利格列汀低剂量组及高剂量组,后3组通过将钛颗粒悬浊液注射至颅骨表面建立颅骨骨溶解模型,从造模后第2天开始,利格列汀低、高剂量组分别灌胃利格列汀(2,10 mg/kg),每天1次,造模3周后,检测血清巨噬细胞极化标志蛋白及炎性因子水平,收集颅骨进行micro-CT扫描、骨参数分析及苏木精-伊红染色评估骨溶解及形态学变化。结果与结论:①细胞实验:与M1诱导组比较,利格列汀低、高剂量组可显著抑制巨噬细胞的M1极化、促进M2极化(P<0.01),且以高剂量组效果更显著(P<0.01)。与破骨诱导组比较,利格列汀低、高剂量组可抑制破骨细胞的活化及骨质吸收,且以高剂量组抑制更显著。与对照组比较,M1诱导组炎性因子mRNA表达升高(P<0.01),而与M1诱导组相比较,利格列汀低、高剂量组炎性因子mRNA表达显著降低(P<0.01)。与对照组比较,破骨诱导组破骨功能标志物的mRNA表达升高(P<0.01);与破骨诱导组比较,利格列汀低、高剂量组破骨功能标志物的mRNA表达降低(P<0.01),且以高剂量组降低更明显。②动物实验:钛颗粒植入导致小鼠颅骨骨溶解破坏,利格列汀可抑制钛颗粒诱导的骨溶解,其中以高剂量组抑制作用更显著。结果表明利格列汀具有调节巨噬细胞极化、抑制破骨细胞活化及对骨骼系统的保护作用。

达格列净联合利格列汀治疗2型糖尿病合并早期糖尿病肾病的临床疗效研究

目的探讨达格列净联用利格列汀在2型糖尿病合并早期糖尿病肾病中的临床治疗效果。方法选取2021年4月—2023年4月新会区人民医院收治的76例2型糖尿病合并早期糖尿病肾病患者为研究对象,根据治疗方法的不同分为两组,观察组(39例)应用达格列净联合利格列汀治疗,对照组(37例)应用格列齐特缓释片+盐酸二甲双胍缓释片治疗,治疗3个月后比较两组患者的空腹血糖、糖化血红蛋白、血肌酐、24 h尿微量白蛋白、肾小球滤过率及不良反应发生情况。结果治疗后,两组空腹血糖及糖化血红蛋白水平均低于治疗前,差异有统计学意义(P均<0.05)。治疗后,对照组空腹血糖水平低于观察组,差异有统计学意义(P<0.05)。对照组治疗后24 h尿微量白蛋白、血肌酐及肾小球滤过率与治疗前比较,差异无统计学意义(P均>0.05);而观察组治疗后24 h尿微量白蛋白较治疗前减少,血肌酐较治疗前下降,肾小球滤过率较治疗前升高,差异有统计学意义(P均<0.05)。两组患者均未发生严重不良反应。结论达格列净联用利格列汀2型糖尿病合并早期糖尿病肾病的治疗中既能良好控制血糖,也能使尿蛋白减少、改善肾功能。

尿毒清颗粒辅助治疗糖尿病肾病的效果

目的 观察尿毒清颗粒辅助治疗糖尿病肾病(DN)的效果。方法 选取成都医学院第二附属医院2021年3月至2022年12月收治的96例DN患者,按随机数字表法将其分为西医组(给予常规治疗及利格列汀)和中西医结合组(西医组基础上给予尿毒清颗粒治疗),各48例。评价两组临床疗效。比较两组治疗前后血糖指标[空腹血糖(FBG)、餐后2 h血糖(2h PBG)、糖化血红蛋白(HbA_(1c))],肾功能指标[血肌酐(Cr)、尿素氮(BUN)、肾小球滤过率(GFR)、24 h尿微量白蛋白、尿液中微量白蛋白与肌酐比值(UA/CR)水平],炎症因子[肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)、γ干扰素(IFN-γ)]和血清磷脂酰肌醇3激酶(PI3K)、Akt激酶和哺乳动物雷帕霉素靶蛋白(mTOR)水平。比较不良反应发生率。结果 中西医结合组临床疗效优于西医组,差异有统计学意义(P<0.05)。治疗后,两组FBG、2h PBG和HbA_(1c)较治疗前降低,且中西医结合组低于西医组,差异有统计学意义(P<0.05)。治疗后,两组Cr、BUN、24 h微量白蛋白尿和UA/CR水平较治疗前降低,GFR水平较治疗前升高,且中西医结合组Cr、BUN、24 h微量白蛋白尿和UA/CR水平低于西医组,GFR水平高于西医组,差异有统计学意义(P<0.05)。治疗后,两组TNF-α、ICAM-1、IFN-γ、PI3K、Akt、mTOR水平均较治疗前降低,且中西医结合组低于西医组,差异有统计学意义(P<0.05)。两组不良发应总发生率比较,差异无统计学意义(P>0.05)。结论 尿毒清颗粒辅助治疗DN患者效果确切,能有效改善患者肾功能,减轻炎症反应和调节PI3K、Akt、mTOR水平,值得应用。

DPP-4 Inhibitor Linagliptin is Neuroprotective in Hyperglycemic Mice with Stroke via the AKT/mTOR Pathway and Anti-apoptotic Effects

Dipeptidyl peptidase 4 (DPP-4) inhibitors have been shown to have neuroprotective effects in diabetic patients suffering from stroke, but less research has focused on patients with mild hyperglycemia below the threshold for a diagnosis of diabetes. In this investigation, a hyperglycemic mouse model was generated by intraperitoneal injection of streptozotocin and then subjected to focal cerebral ischemia. We demonstrated that the DPP-4 inhibitor linagliptin significantly decreased the infarct volume, reduced neuronal cell death, decreased inflammation, and improved neurological deficit compared with control mice. Linagliptin up-regulated the expression of p-Akt and p-m TOR and regulated the apoptosis factors Bcl-2, Bax, and caspase 9. Taken together, these results suggest that linagliptin exerts a neuroprotective action likely through activation of the Akt/m TOR pathway along with anti-apoptotic and anti-inflammatory mechanisms.Therefore, linagliptin may be considered as a therapeutic treatment for stroke patients with mild hyperglycemia.

格列美脲联合利格列汀对2型糖尿病患者糖脂代谢和体重指数及心血管事件发生率的影响

目的探讨格列美脲联合利格列汀对2型糖尿病(diabetes mellitus type 2,T2MD)患者糖脂代谢、体重指数(body mass index,BMI)及心血管事件发生率的影响。方法选取2020年10月至2021年10月长春市中心医院收治的84例T2MD患者作为研究对象,采用随机信封法分为参照组与联合组,每组42例。参照组采用口服格列美脲治疗,联合组采用格列美脲联合利格列汀治疗。比较两组治疗前后糖脂代谢情况、BMI变化情况及心血管事件发生率。结果治疗后,两组空腹血糖(fasting blood glucose,FPG)及餐后2 h血糖(2 h postprandial blood glucose,2 h PG)、糖化血红蛋白A1c(glycosylated hemoglobin A1c,HbAlc)、血糖标准差(standard deviation of blood glucose,SDBG)、平均血糖波动幅度(mean amplitude of glycemic excursions,MAGE)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)及低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平均低于治疗前,且联合组低于参照组,差异有统计学意义(P<0.05)。治疗3、6个月后,两组BMI均低于治疗前,且联合组低于参照组,差异有统计学意义(P<0.05)。随访期间,联合组心血管事件发生率低于参照组,差异有统计学意义(P<0.05)。结论格列美脲联合利格列汀治疗能有效调节T2MD患者糖脂代谢,降低BMI和心血管事件发生率,值得临床推广应用。

Effects of linagliptin on inflammatory factors and arteriosclerosis in patients with newly diagnosed type 2 diabetes mellitus

In the present study,we aimed to investigate the effects of linagliptin on inflammatory factors and carotid intima-media thickness(CIMT)in newly diagnosed type 2 diabetes mellitus(T2 DM)patients with carotid atherosclerotic disease(CAD).A total of 326 patients with newly diagnosed T2 DM complicated with CAD were randomly divided into two groups.There were 163 patients in the control group,who were treated with metformin monotherapy.There were 163 patients in the experimental group,who were treated with metformin in combination with linagliptin.The CIMT before and after treatment was measured by color Doppler ultrasound,and the contents of IL-6 and IL-1βbefore and after treatment were detected by ELISA.The levels of inflammatory factors and CIMT before and after treatment were compared between the two groups,and the correlation between IL-6,IL-1βand CIMT was studied.After 24 weeks of treatment,the levels of inflammatory factors and CIMT in the experimental group were significantly lower compared with the control group(P<0.01),and the serum levels of IL-6 and IL-1βwere positively correlated with CIMT.In the present study,we concluded that linagliptin could improve the levels of inflammatory factors and CIMT in newly diagnosed T2 DM patients with CAD,and IL-6 and IL-1βmight participate in the occurrence and development of CAD by influencing CIMT.

Cardioprotective effect of Linagliptin on diabetic Wistar rats

Diabetic cardiomyopathy(DCM)is an important cardiovascular complication of diabetes mellitus,while the pathogenesis of DCM has not been fully elucidated.In the present study,we aimed to investigate the effect of Linagliptin on cardiomyocytes of diabetic rats and its mechanism.Cardiac function was evaluated by two-dimensional ultrasound at different time points for each group.HE staining was used to evaluate myocardial injury and inflammatory condition.Sirius-red staining was used to observe the degree of myocardial fibrosis under optical microscope.TUNEL staining was used to investigate the degree of cardiomyocyte apoptosis in four groups.The expressions of m RNAs in relevant cells,including Bcl-2,Bax,TNF-α,PAI-1,CTGF and TGF-β1,were measured by reverse transcription polymerase chain reaction(RT-PCR)and Western blotting analysis in different groups.The expression and transcriptional function of Nrf2 in myocardium activated by Lingliptin were determined using RT-PCR,Western blotting analysis and immunofluorescence.The results showed that the left ventricular volume(LV),left ventricular thickness(LT),fasting blood glucose(FBG)and heart weight/body weight(HW/BW)in diabetes and Linagliptin CO treatment group were significantly lower compared with diabetic group(P<0.05),while the ejection fraction(EF)was higher compared with diabetic group(P<0.05).From HE staining,the treatment of Linagliptin made the arrangement of myocardial fibers more regular,and the striation of myocardial cells became clearer.The Sirus-red staining showed that there was significant accumulation of collagen in the diabetic group rats,indicating that the rats in diabetic group had cardiac fibrosis.The phenomenon in diabetes and Linagliptin CO treatment group was alleviated.TUNEL staining showed that at time point of 4 weeks,the degree of cardiomyocyte apoptosis in diabetes and Linagliptin CO treatment group was lower compared with diabetic group(P<0.01).The expressions of cleaved-caspase-3,TNF-α,PAI-1,CTGF and TGF-β1 proteins in diabetic rats were significantly decreased by Linagliptin,and the difference was statistically significant(cleaved-caspase-3:P<0.01;TNF-α:P<0.01;PAI-1:P<0.05;CTGF:P<0.05;TGF-β1:P<0.05).Compared with the diabetic group,the ratio of Bcl-2/Bax was inecreased in diabetes and Linagliptin CO treatment group,and the difference was statistically significant(P<0.05).From Nrf2 expression in the nucleus and cytosol by RT-PCR,Western blotting analysis and immunofluorescence test,the results showed that Linagliptin promoted the Nrf2 nuclear translocation in myocardial tissue cells.The expression of Nrf2 was significantly down-regulated in the heart of diabetic rats(P<0.01),while this phenomenon in diabetes and Linagliptin CO treatment group was greatly ameliorated.This paper studied the effect of Linagliptin on diabetic myocardial injur and found that the protective mechanism might be related to Nrf2 signaling pathway of antioxidant stress.Collectively,our finding provided new ideas and therapeutic targets for the prevention and treatment of DCM.

抗糖尿病新药Linagliptin的临床研究进展

目的:介绍抗糖尿病新药Linagliptin的临床研究进展。方法:根据文献,综述该药的理化性质及临床研究进展。结果与结论:Linagliptin是一种口服有效的具有高选择性的DPP-4抑制剂,单用或与其他经典抗糖尿病药合用,均可有效降低糖化血红蛋白(HbA1c)水平;同时也可有效控制空腹血糖浓度和餐后2h血糖浓度,且肝功能下降和肾功能不全的2型糖尿病患者的给药剂量无需调整。在安全性、有效性及耐受性等方面具有独特的优点。

利格列汀多晶型研究

研究了利格列汀复杂的晶型现象及其晶格中的构象变化.通过培养利格列汀的单晶并进行X射线单晶衍射分析,首次得到了包括晶型A在内的3种晶体结构;结合文献已报道的2种晶体结构,分析了各晶体结构的特点及其晶格中的分子构象.研究结果表明,5种晶体里存在晶型A和晶型F两种晶型,其中晶型F为准多晶型,可以包含多种溶剂,形成通道型溶剂合物,其晶格参数随包含的溶剂略有变化.晶型A的构象与晶型F的构象存在较高能垒,导致2种晶型难以互相转化.晶型F不同溶剂合物之间的分子构象并不完全相同,在粉末X射线衍射(PXRD)谱图上也有显著差异.最后,通过混悬转晶和热分析等方法研究了晶型之间的转化关系.

利格列汀联合二甲双胍治疗T2DM合并血脂异常患者对糖脂代谢和胰岛β细胞功能指标的影响

目的探究利格列汀联合二甲双胍治疗2型糖尿病(T2DM)合并血脂异常患者对糖脂代谢和胰岛β细胞功能指标的影响。方法选取2020年5月—2022年10月本院就诊的153例T2DM合并血脂异常患者作为观察对象,采用简单随机化法分为观察组76例和对照组77例。对照组采用二甲双胍进行治疗,观察组在其基础上给予利格列汀。比较两组治疗前、治疗5个月后血糖水平[空腹血糖(FPG)、餐后2h血糖(2hPBG)]、血脂水平[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、胰岛细胞功能[空腹胰岛素、胰岛素样生长因子1(IGF-1)、胰岛素抗体(IAA)]的变化。结果治疗5个月后,两组FPG、2hPBG、TC、TG、LDL-C均显著降低,且观察组低于对照组(P<0.05);治疗5个月后,两组HDL-C、空腹胰岛素、IGF-1均显著升高,且观察组高于对照组(P<0.05)。结论利格列汀联合二甲双胍的临床疗效显著,可有效改善T2DM合并血脂异常患者糖脂代谢过程,对于患者恢复有利。

利格列汀片联合黄葵胶囊治疗对早期糖尿病肾病患者CysC、Hcy的影响

目的观察早期糖尿病肾病患者采取利格列汀片联合黄葵胶囊进行治疗对其胱抑素C(CysC)以及同型半胱氨酸(Hcy)的影响。方法回顾性收集70例早期糖尿病肾病患者临床资料作为研究对象,根据治疗方案的不同将其分为对照组和研究组,每组35例。对照组应用利格列汀片治疗,研究组接受利格列汀片联合黄葵胶囊治疗。对比两组治疗前后CysC以及Hcy水平改变情况。结果研究组治疗后的CysC(1.14±0.23)mg/L、Hcy(9.25±1.75)μmol/L显著低于对照组的(1.82±0.63)mg/L、(12.84±2.26)μmol/L,对比存在统计学差异(P<0.05)。结论为早期糖尿病肾病患者提供利格列汀片联合黄葵胶囊治疗,能够有效降低CysC以及Hcy水平,提升疾病治疗效果。