Effects of co-administration of methanol leaf extract of Catharanthus roseus on the hypoglycemic activity of metformin and glibenclamide in rats

Objective:To investigate the interacting effects of co-administration of methanol leaf extract of Catharanthus roseus（C.roseus） on the hypoglycemic activity of metformin as well as glibenclamide using experimental rats.Methods:Phytochemical analysis as well as acute toxicity and lethality(LD50) test were carried out on its methanol leaf extract.The alloxan model for experimental induction of diabetes in rats was employed.Six groups comprising five rats each were used.GroupsⅡ,ⅢandⅣreceived 250 mg/kg of extract,100 mg/kg of metformin and 1 mg/kg of glibenclamide respectively,while V and VI were administered metformin-extract and glibenclamide-extract combinations respectively at doses as above.Group I served as negative control and received only distilled water.All administration was done once daily for seven days. Fasting blood glucose was determined at 2,12,24,72 and 168 h using a glucometer.One-way ANOVA with post-hoc tests was used to assess for significant difference due to administration of drug alone and with co-administration of drug and extract.Results:The LD50 was 2 121.32 mg/kg. The phytochemical studies indicated the presence of saponins,tannins,alkaloids,phlotatannins, flavonoids,triterpenoids,reducing sugars,anthraquinones and glycosides.All medicaments significantly reduced blood glucose levels when compared with control alone（P【0.05） with the highest percentage reduction in blood glucose（64.86%） exhibited by metformin-extract combination.Conclusions:The leaf extract of C.roseus significandy increases the hypoglycemic effect of metformin.

Effects of long-term monotherapy with glimepiride vs glibenclamide on glycemic control and macrovascular events in Japanese Type 2 diabetic patients

We investigated whether long-term glimepiride (GP) monotherapy improves insulin resistance and exerts a beneficial effect on beta cell function, as compared with glibenclamide (GC). One hundred Japanese Type 2 diabetic patients were randomly assigned to the GP (n = 50) or the GC (n = 50) group. During a 5-year monitoring period, patients received the indicated SU monotherapy, while changes in SU doses were allowed as needed to maintain HbA1C below 7.0%. The GC group, in parallel with fasting insulin, showed a rapid homeostatic model assessment (HOMA)-R increase and maintained a high HOMA-R level. In contrast, HOMA-R in the GP group decreased continuously, from 2.9 at baseline to 1.8 at study completion. In the GC group, HOMA-b was markedly increased in the first 6 months, then gradually decreased through 18 months. While the HOMA-β elevation in the GP group was more moderate than that in the GC group, HOMA-β levels were maintained with a slight decrease. The cumulative macrovascular disease outcome was 1 for the GP and 7 for the GC group, showing a significant difference. These results suggest that glimepiride monotherapy markedly improved HOMA-R with moderate insulin stimulation, which may account for the difference in macrovascular disease development as compared with the group receiving glibenclamide.

Autophagy induced by glibenclamide serves as a defense against apoptosis in INS-1 rat insulinoma cells

Glibenclamide, a blocker of ATP-sensitive potassium channels, has been found to induce apoptosis in some cell types, including pancreatic beta-cells. Since autophagy plays doubleedged roles in pancreatic beta-cell survival, frequently through cross-talking with apoptosis, we investigated if glibenclamide induced autophagy in INS-1 rat insulinoma cells and the influence of autophagy on apoptosis. Mammalian target of rapamycin (mTOR) is a negative regulator of autophagy. As one of the substrates of mTOR, p70 S6 kinase (p70 S6K) is phosphorylated upon mTOR activation. Our results showed that glibenclamide induced an elevated protein level of the autophagy marker LC3-II, while decreasing phosphorylated p70 S6K, indicative of inhibition on mTOR signaling in INS-1 cells. Furthermore, inhibiting glibenclamide-induced autophagy via knocking down the autophagy essential gene Atg7 decreased cell viability and increased apoptosis in INS-1 cells. Our results indicate that glibenclamide induces autophagy in INS-1 cells, and that autophagy activation is exerting a protective activity against apoptosis.

Effect of 'Double C' therapy combined with glibenclamide in the treatment of GDM patients and its influence on serum omentin-1 and VF levels

Objective: To analyze the effect of 'double C' therapy combined with glibenclamide in the treatment of GDM and its influence on serum omentin-1 and VF levels. Methods: 100 patients with GDM admitted to our hospital from January 2016 to May 2018 were randomly divided into observation group and control group. The control group was treated with routine treatment, while the observation group was treated with 'double C' therapy combined with glibenclamide. Blood sugar level, cesarean section rate, premature delivery rate, pregnancy-induced hypertension rate, fetal distress and incidence of macrosomia were investigated. The levels of omentin-1 and VF in serum were measured. Results: The levels of HbA1c, FPG, 1 h PBG and 2 h PBG in blood of the two groups before delivery were significantly lower than those of the control group (P<0.05), and the levels of HbA1c, FPG, 1 h PBG and 2 h PBG in the observation group were significantly lower than those in the control group (P<0.05);the levels of omentin-1 and VF in the two groups before delivery were significantly higher (P<0.05), and the levels of omentin-1 in the observation group were significantly higher than those in the control group (P<0.05). After treatment, the rate of cesarean section, premature delivery, pregnancy-induced hypertension, fetal distress and macrosomia in the observation group were higher than those in the control group, and the difference was statistically significant (P<0.05). Conclusions: The combination of double C therapy and glibenclamide can improve the curative effect of GDM and the levels of omentin-1 and VF in blood.

Optimization of Isolation and Identification Conditions of Glibenclamide Annotation

A method for dispersive liquid-liquid microextraction of glibenclamide on model mixtures with urine has been developed. The extraction conditions have been optimized and the influence of extractants and dispersing agent for allocation of toxicant from biosubstrate has been experimentally established. The method of TLC （thin layer chromatography） screening in order to remove endogenous and exogenous substances has been developed. The method of IR-spectroscopy for confirmatory analysis has been used. The combination of the two methods of analysis allows identifying glibenclamide quickly and reliably isolated from bioliquid and reducing the risk of false-positive results.

Effects of low dose Glibenclamide on secondary damage after acute spinal cord injury in rats

Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated

Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood-brain barrier dysfunction

Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently,especially in warfarin-associated intracerebral hemorrhage(W-ICH).In the present study,we employ the warfarin-associated intracerebral hemorrhage(W-ICH)rat model,to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage,hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage.Methods In the present study,we tested whether glibenclamide,a common hypoglycemic drug,could attenuate hematoma expansion in a rat model of W-ICH.Hematoma expansion was evaluated using magnetic resonance imaging;brain injury was evaluated by brain edema and neuronal death;and functional outcome was evaluated by neurological scores.Then blood-brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein.Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH,thus mitigating brain edema and neuronal death and promoting neurological function recovery,which may benefit from alleviating blood-brain barrier disruption by suppressing matrix metallopeptidase-9.Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH.

Administration of Fenugreek Seed Extract Produces Better Effects in Glibenclamide-Induced Inhibition in Hepatic Lipid Peroxidation: An in vitro Study

Objective: To evaluate the comparative effects of fenugreek(Trigonel a foenum graecum) seed extract(FSE) alone and in combination with an antidiabetic conventional medicine,glibenclamide(GLB),on the inhibition of in vitro lipid peroxidation(LPO) in liver,the major target organ of a drug.Methods: LPO was induced by ferrous sulphate(Fe So4),hydrogen peroxide(H2 O2) and carbon tetrachloride(CCl4) and the effects of test seed extract and/or GLB were evaluated.Results: While Fe So4,H2 O2 and CCl4 markedly enhanced the hepatic LPO,simultaneous administration of FSE reduced it in a concentration dependent manner.However,when both FSE and GLB were added to the incubation mixture,chemical y induced hepatic LPO was further inhibited.The test extract also exhibited high antioxidative activity in 1,1-diphenyl-2-picrylhydrazyl radical and in 2,2'-azino-bis,3-ethylbenzothiazoline-6-sulphonic acid radical scavenging assays.Conclusion: FSE therapy in moderate concentration along with a hypoglycemic drug may prove to be advantageous in ameliorating diabetes mel itus and other diseases that are LPO mediated.

Changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus

The aim of this study was to investigate the pharmacokinetics of glibenclamide(Gli)administrated orally and intravenously to normal and diabetic rats.The AUC(0–720 min)of orally administered Gli in diabetic rats(321.24 mg min/L)was greater than that(57.752 mg min/L)in normal rats.CL(0.019 L/min/kg)was significantly slower than that(0.092 L/min/kg)of normal rats.The AUC(0–480min)of intravenous Gli in diabetic rats(1528.280 mg min/L)also was significantly greater than that(509.523 mg min/L)in normal rats,and CL was decreased approximately 3-fold.No significant difference in intestinal absorption of Gli was observed between normal and diabetic rats as determined by in situ single-pass intestinal perfusion.The clearance of Diclofenac(a substrate of CYP2C9)was determined to evaluate changes in hepatic drug-metabolizing enzyme activity in rats.The CL in diabetic rats was significantly lower(42.43%decrease)than that in normal rats.Hepatic protein expression of CYP2C9 was measured using Western blot analysis;compared with normal rats,the hepatic protein expression of CYP2A9 was decreased in diabetic rats.Therefore,the slower clearance of Gli in diabetic rats can be attributed primarily to the lower expression of hepatic CYP2C9.

Hypoglycemic efficacy of Ocimum gratissimum and Vernonia amygdalina compared with insulin and glibenclamide in type Ⅰ and type Ⅱ diabetic rat models

Objective: To compare the efficacy of Ocimum gratissimum (O. gratissimum) and Vernonia amygdalina (V. amygdalina) with those of insulin and glibenclamide.Methods: Type Ⅰ and Ⅱ diabetes mellitus (DM) were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin and intraperitoneal administration of nicotinamide (100 mg/kg) along with streptozotocin, respectively. The state of diabetes was confirmed weekly by testing blood glucose level using a glucometer.Results: The weekly blood glucose levels were higher in type I DM than in type Ⅱ DM. Type Ⅰ DM plus O. gratissimum showed a weekly progressive significant reduction in blood glucose compared to type Ⅰ DM control. Type Ⅰ DM control showed a duration dependent significant higher blood glucose concentration compared to normal control. Type I DM plus V. amygdalina also showed a time dependent significant lower glucose level compared to normal control and type Ⅰ DM control. Combination treatment of type Ⅰ DM (O. gratissimum plus V. amygdalina) showed a significantly elevated glucose concentration compared to normal control which was similar to type I DM control. Insulin treatment in type I DM showed a weekly progressive significant reduction of glucose concentration compared to normal control and type I DM control. Type Ⅱ DM control showed a fairly constant blood glucose concentration throughout the duration of treatment that was significantly higher than that of the normal control. Type Ⅱ DM plus O. gratissimum showed a fairly steady significant reduction of glucose concentration compared to type Ⅱ DM control and normal control. Type Ⅱ DM plus V. amygdalina also showed a fairly constant significant reduction of glucose concentration compared to type Ⅱ DM control and normal control. Type II DM (O. gratissimum plus V. amygdalina) showed a slightly progressive significant reduction of glucose concentration compared to normal control and type Ⅱ DM control. Type Ⅱ DM with glibenclamide showed almost steady significant reduction in glucose concentration compared to normal control and type Ⅱ DM control. Conclusions: From the result, it is evident that O. gratissimum and V. amygdalina administration produces more potent hypoglycemic activity than insulin and glibenclamide in type I and Ⅱ DM models, respectively.

UV Spectroscopic Method for Optimization and Determination of Glibenclamide in Bulk,Pharmaceutical Dosage Form and its Application for In Vitro Interaction Studies

A simple,easy and cost-efficient UV spectroscopic method was developed and validated for glibenclamide,the second generation of sulfonylureas,using 0.1 N NaOH as a solvent.The proposed method is linear(R^(2)>0.999)with the range 5-25μg mL^(−1),accurate(99.60%),precise(inter and intraday variation 0.241 and 0.019%,respectively)and robust(<1%).The quantification and detection limit were 1.46 and 0.48μg mL^(−1),respectively.The validated method was applied for in vitro interaction studies of glibenclamide(GLB)with commonly prescribed quinolones(ciprofloxacin,levofloxacin,moxifloxacin,and gemifloxacin)and nonsteroidal anti-inflammatory drugs(NSAIDs)(diclofenac sodium,ibuprofen,mefenamic acid,and aspirin)using UV spectrophotometer.The in vitro interaction studies were carried out in different artificially prepared physiological buffers at 37°C for 2 h.Results showed raised level of glibenclamide when interacted with gemifloxacin(pH 7.4),levofloxacin(pH 9),ciprofloxacin(pH 4.5)and with moxifloxacin(pH 4.5,7.4 and 9).Interaction with NSAIDs results in increased%availability of glibenclamide in the presence of diclofenac sodium,ibuprofen,and mefenamic acid at pH 4.5.The anticipated method can be successfully applied for the routine analysis and also for the interaction of glibenclamide with other drugs.

长效胰岛素联合口服降糖药治疗2型糖尿病的疗效

目的 分析2型糖尿病(T2DM)采取长效胰岛素+口服降糖药治疗的效果。方法 96例T2DM患者,随机分为观察组和对照组,每组48例。对照组给予口服降糖药治疗,观察组给予长效胰岛素+口服降糖药治疗。比较两组患者治疗前后的血糖[糖化血红蛋白(HbA1c)、餐后2 h血糖(2 h PG)、空腹血糖(FPG)]水平、生活质量(总体健康、精力、社会功能、心理健康、躯体疼痛、躯体角色功能、情绪角色功能、躯体健康)评分以及不良反应发生情况(体重增加、低血糖)、治疗效果。结果 治疗后,观察组患者HbA1c(6.20±0.91)%、2 h PG(8.63±1.37)mmol/L、FPG(5.83±0.72)mmol/L均低于对照组的(8.34±1.15)%、(9.56±1.60)mmol/L、(7.91±1.31)mmol/L,差异具有统计学意义(P<0.05)。观察组不良反应发生率2.08%(1/48)低于对照组的14.58%(7/48),差异具有统计学意义(χ^(2)=4.909,P<0.05)。治疗后,观察组患者总体健康评分(63.25±4.48)分、精力评分(74.25±4.54)分、社会功能评分(83.67±3.91)分、心理健康评分(81.48±4.25)分、躯体疼痛评分(74.48±6.38)分、躯体角色功能评分(73.54±4.18)分、情绪角色功能评分(84.54±3.67)分、躯体健康评分(71.37±4.28)分;对照组患者总体健康评分(54.54±3.25)分、精力评分(61.22±4.01)分、社会功能评分(76.32±2.75)分、心理健康评分(61.24±3.75)分、躯体疼痛评分(66.58±4.70)分、躯体角色功能评分(61.24±4.42)分、情绪角色功能评分(73.05±2.50)分、躯体健康评分(52.31±2.76)分。观察组患者总体健康、精力、社会功能、心理健康、躯体疼痛、躯体角色功能、情绪角色功能、躯体健康评分均高于对照组,差异有统计学意义(P<0.05)。观察组治疗总有效率95.83%高于对照组的79.17%,差异具有统计学意义(P<0.05)。结论 长效胰岛素联合口服降糖药物对T2DM治疗可有效改善血糖水平,降低不良反应发生率,提升疗效。

格列本脲治疗4例新生儿糖尿病的疗效分析

目的探讨格列本脲治疗新生儿糖尿病的临床效果。方法选取4例新生儿糖尿病患儿为研究对象,患儿入院后进行血常规、血气分析[血液酸碱度(pH)、剩余碱(BE)、碳酸氢根(HCO3-)]、尿常规、静脉血糖、C-肽、糖化血红蛋白指标及基因检测。给予患儿格列本脲治疗,随访3 a,观察并分析其疗效。结果病例1、4 KCNJ11基因编码区存在c.602G>A突变,病例2、3 ABCC8基因编码区存在c.4106G>T突变。治疗后,4例患儿血常规、血气分析、尿酮体以及静脉血糖、C-肽、糖化血红蛋白均正常。未出现低血糖及酮症酸中毒反应,无智力和生长发育异常。定期进行肝、肾功能检查,均正常。末次随访,生长发育与同龄人相仿。结论格列本脲治疗新生儿糖尿病可降低血糖水平,疗效确切,安全性高。

格列本脲联合二甲双胍治疗妊娠期糖尿病治疗的临床效果及对妊娠结局影响

目的探讨格列本脲联合二甲双胍治疗妊娠期糖尿病(GDM)的临床效果,并分析对妊娠结局的影响。方法选取本院2022年3月—2023年2月的86例GDM患者为研究对象,并采用随机数字表法分组,各43例。对照组以二甲双胍治疗,观察组以格列本脲联合二甲双胍治疗。比较两组血糖控制效果、血脂水平、氧化应激水平、不良妊娠结局、新生儿不良结局。结果治疗后观察组空腹血糖和餐后2 h血糖等指标水平均低于对照组(均P<0.05);治疗后观察组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平均低于对照组,高密度脂蛋白胆固醇(HDL-C)水平高于对照组(均P<0.05);治疗后观察组丙二醛(MDA)水平低于对照组,超氧化物歧化酶(SOD)水平高于对照组(均P<0.05);两组不良妊娠结局和新生儿不良结局发生率对比差异均无统计学意义(均P>0.05)。结论格列本脲联合二甲双胍治疗GDM的血糖控制效果显著,并且有助于调整血脂、氧化应激水平,且不会增加不良妊娠结局的发生。

塞来昔布联合格列本脲在糖尿病性骨关节病治疗中的价值研究

目的探究糖尿病性骨关节病治疗中应用塞来昔布联合格列本脲的价值。方法选取南安市医院于2023年4月—2024年5月收治的118例糖尿病性骨关节病患者为研究对象,按照不同治疗方法分为对照组(阿卡波糖联合塞来昔布治疗)和观察组(塞来昔布联合格列本脲治疗),各59例,对比两组血糖水平、症状改善程度及炎症因子水平。结果治疗后,观察组空腹血糖、餐后2 h血糖水平均低于对照组,差异有统计学意义(P均<0.05)。治疗后,观察组白细胞介素-6、肿瘤坏死因子-α及C反应蛋白水平均低于对照组,差异有统计学意义(P均<0.05)。观察组关节肿胀、关节疼痛、关节活动受限及关节晨僵时间均短于对照组,差异有统计学意义(P均<0.05)。结论实施塞来昔布联合格列本脲应用于糖尿病性骨关节病治疗中,可改善其血糖水平,减少不良反应的发生,提升整体疗效。

门冬胰岛素与格列本脲联用治疗对老年糖尿病患者血糖指标及不良反应情况的影响

目的:探对老年糖尿病患者予以门冬胰岛素与格列本脲联用治疗对血糖指标及不良反应情况的影响。方法:纳入我院2021年3月至2023年3月收治的100例糖尿病患者,随机分组,各50例,对照组予以门冬胰岛素治疗,观察组基于门冬胰岛素联合格列本脲治疗,观察两组糖代谢及及胰岛β细胞功能变化状况,检测两组半胱氨酸(HCY)、胱抑素C(CysC)、半乳糖血症(GAL)、鸢尾素(Irisin)指标水平,详细统计不良反应发生情况。结果:治疗前两组糖代谢水平无显著差异(P>0.05)。治疗后,观察组FPG、2hPG和HbAlc水平均低于对照组(P<0.05);治疗前两组胰岛β细胞功能无显著性差异(P>0.05),观察组治疗后HOMA-βI30水平/△G30显著高于对照组,HOMA-IR和FINS水平显著低于对照组(P<0.05);组间HCY、CysC、GAL及Irisin水平对比,干预前组间数据无明显差异(P>0.05),干预后观察组HCY、CysC和GAL水平均显著低于对照组,而其Irisin水平明显高于对照组(P<0.05);组间不良反应对比可见,观察组发生率显著低于对照组(P<0.05)。结论:门冬胰岛素联合格列本脲的治疗方案应用在老年糖尿病患者中对胰岛素敏感性的提升有积极作用,促进机体糖代同时可有效控制血糖水平。

格列本脲联合医学营养支持对妊娠期糖尿病患者血糖控制和妊娠结局的影响

目的观察妊娠期糖尿病患者联合应用格列本脲、医学营养支持治疗的临床效果。方法选取2022年1月—2023年1月我院收治的80例妊娠期糖尿病患者为研究对象,按随机数字表法将其分为对照组和观察组,各40例。入院后均进行常规基础治疗,在此基础上对照组配合医学营养支持治疗,观察组配合医学营养支持治疗同时加用格列本脲。比较两组的血糖控制优良率、孕期体质量、血糖水平、胰岛素水平、妊娠结局、新生儿结局。结果观察组患者血糖控制优良率为92.50%,高于对照组的72.50%,差异有统计学意义(P<0.05)。治疗前,两组患者孕期体质指数(BMI)、空腹血糖(FPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)水平比较,组间差异无统计学意义(P>0.05);治疗后,观察组患者孕期BMI(26.03±1.52)kg/m^(2)、FPG(6.23±0.99)mmol/L、FINS(11.01±1.62)mU/L、HbA1c(6.16±0.71)%均低于对照组的(28.61±1.73)kg/m^(2)、(7.74±0.91)mmol/L、(13.76±1.58)mU/L、(7.08±0.75)%,组间差异有统计学意义(P<0.05)。观察组患者早产率22.50%、剖宫率32.50%、羊水异常率12.50%、胎膜早破发生率17.50%、产后出血发生率22.50%、产褥感染发生率15.00%均低于对照组的45.00%、55.00%、32.50%、37.50%、50.00%、37.50%,组间差异有统计学意义(P<0.05)。观察组胎儿宫内窘迫发生率10.00%、新生儿窒息发生率2.50%、新生儿低血糖发生率7.50%、新生儿感染发生率5.00%、新生儿高胆红素血症发生率2.50%均低于对照组的32.50%、20.00%、30.00%、25.00%、22.50%,组间差异有统计学意义(P<0.05)。结论妊娠期糖尿病患者在医学营养支持治疗基础上加用格列本脲,能够显著提高血糖控制效果,改善孕期体质量,降低空腹胰岛素水平,优化妊娠结局,提升人口出生质量。

细胞色素P450 CYP2C9＊3对格列本脲和氯诺昔康中国人体药代动力学的影响

目的研究人体内细胞色素P4502C9酶突变等位基因CYP2C93对格列本脲和氯诺昔康药代动力学的影响。方法采用PCRRFLP方法对83名无血源关系的受试者进行CYP2C93等位基因的筛查,基因型为CYP2C91/3(n=7)和1/1(n=11)的受试者分别参加了格列本脲和氯诺昔康的人体药代动力学试验。采用LC/MS/MS法分别测定受试者口服格列本脲(2.5mg)和氯诺昔康(8mg)后不同时刻血浆中格列本脲和氯诺昔康的浓度。结果两组受试者口服格列本脲后,CYP2C91/3组AUC0∞显著增加,为CYP2C91/1组的1.5倍,CL/F降低了40%;两组受试者口服氯诺昔康后,CYP2C91/3组AUC0∞亦显著增加,为CYP2C91/1组的2.2倍,CL/F降低了55%。结论CYP2C9酶的突变等位基因CYP2C93对格列本脲和氯诺昔康的药代动力学有显著性影响。

油茶皂苷对缺氧复氧所致大鼠心脏损伤的保护作用及其机制探讨

目的 :通过大鼠离体心脏 L angendoff灌流 ,观察油茶皂苷 (sasanquqsaponin,SQS)对缺氧复氧 (anoxia/reoxygenation,A/ R)损伤的保护作用及其机制。方法 :A/ R为缺氧 40 m in再给氧 30 min;SQS0 .5 mg/ L 或Gliberclam ide30 μmol/ L + SQS0 .5 mg/ L 于缺氧复氧前 15 min灌流 15 m in,分别记录心功能及测量酶活性。结果 :与 A/ R组相比 ,SQS组能增加心肌的收缩功能 ,使氧自由基清除剂超氧化物歧化酶 (SOD) ,谷胱苷肽转移酶(GSH- Px)活性增强 ,脂质过氧化产物丙二醛 (MDA )生成减少 ,降低心肌组织钙含量 ,使肌酸激酶 (CK )生成减少 ,所以 SQS对心肌 A/ R损伤具有保护作用。在加入 KATP通道阻断剂 Gliberclam ide与 SQS同时灌注时 ,发现 SQS的上述作用消失。结论 :SQS的心肌保护与 KATP通道的开放有关。

高效液相色谱法测定人血浆中格列本脲浓度

目的 :建立测定人血浆中格列本脲浓度的高效液相色谱法。方法 :格列本脲血浆样品在酸性条件下以二氯甲烷 正己烷 ( 5 0∶5 0 )提取 ,以格列齐特为内标。Nova pakC18柱 ( 4 .6mm× 2 5 0mm ,4 μm) ,流动相为乙腈 0 .0 3mol·L-1磷酸二氢钾(pH 3.0 ) ( 4 4∶5 6 ) ,流速 1.2mL·min-1,检测波长 2 2 8nm。结果 :标准曲线线性范围 2 5～ 6 0 0 μg·L-1(r =0 .9992 ) ,血浆中格列本脲最低检测限为 15 μg·L-1。平均提取回收率为 ( 81.9± 3.6 ) % ,平均方法回收率为 ( 10 1.1± 6 .8) % ,日内RSD≤5 .0 % ,日间RSD≤ 9.1%。结论 :该方法具有良好的准确性、精密性和较高的灵敏度 。