目的 研究外源性硫化氢(H2S)通过丝裂原活化细胞外信号调节蛋白激酶(MEK)/细胞外信号调节激酶(ERK)信号通路对早期糖尿病肾脏疾病(DN)大鼠的保护作用.方法 随机选取SPF级健康雄性SD大鼠24只腹腔一次性注射1％链尿佐菌素(STZ)60 mg/kg制作DN模型,余下10只(正常对照组)腹腔一次性注射等量的柠檬酸缓冲液.3周后DN造模成功,再将24只DN大鼠随机分为DN组和DN+硫氢化钠(NaHS)组,每组各12只.DN+NaHS组予腹腔注射NaHS溶液56μmol·kg-1·d-1,正常对照组和DN组予等量生理盐水腹腔注射,3组大鼠均连续注射12周.检测各组血清肌酐(SCr)、尿素氮(BUN)及24小时尿蛋白(24h Upro)水平,观察其肾脏组织病理变化.采用Katafuchi评分评估大鼠肾脏病变(包括肾小球、肾小管及肾血管).采用免疫组化法检测ERK1/2、MEK1和MEK2蛋白阳性区域面积百分比.结果 DN组大鼠SCr、BUN及24h Upro水平、肾脏组织Katafuchi评分、MEK1、MEK2及ERK1/2蛋白阳性区域面积百分比均显著高于正常对照组和DN+NaHS组(P<0.01),而正常对照组与DN+NaHS组大鼠上述指标水平比较差异均无统计学意义(P>0.05).结论 外源性H2S对早期DN大鼠肾脏的保护作用可能与抑制MEK/ERK信号通路有关.

Diabetes mellitus (DM) is a major disease threatening human health and its incidence is increasing year on year. As a chronic complication of DM, hearing loss mostly occurs undetectably. However, the mechanism of this diabetes-related hearing loss (DRHL) remains unclear and there is no effective clinical treatment. Studies of animal or human pathology show that DM causes damage to the blood vessels, spiral ganglion neurons, afferent nerve fibers, the organ of Corti, and the stria vascularis of the inner ear. In recent years, more advances in pathological research have revealed the possible mechanism of DRHL. In addition, a large number of clinical studies suggest that the duration and severity of DM are closely related to the incidence and severity of DRHL. This review focuses on the relationship between DM and hearing loss. The clinical audiological characteristics of diabetic patients, risk factors for DRHL, typical pathology, and potential interventions of DRHL are summarized. This will help reveal the pathogenesis and intervention approaches for DRHL.

Diabetic nephropathy is a microvascular lesion of the kidney in the development of diabetes, which is the most common cause of end-stage renal disease. The pathogenesis of diabetic nephropathy has not been elucidated. Oxidative stress and inflammatory response are believed to play important roles in the pathogenesis. At present, diabetic nephropathy has no relatively effective intervention means. A large number of studies now have proved that the nuclear factor erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathway is an important signaling pathway closely related to the occurrence and development of diabetic nephropathy, participating in the body’s antioxidant stress and anti-inflammatory reactions. It has been found that some active substances of traditional Chinese medicine and compound prescription of traditional Chinese medicine can regulate Nrf2/HO-1 signal pathway to resist oxidative stress and inflammation, thereby improving renal function and delaying renal fibrosis in patients. This article describes the Nrf2/HO-1 signaling pathway and its relationship with DN, and reviews the research progress of traditional Chinese medicine for diabetic nephropathy intervention based on this pathway in recent years.

2型糖尿病(T2DM)是一种中老年高发、病因复杂的慢性代谢性疾病,极易引发血管内皮功能紊乱,进而出现动脉粥样硬化,导致微血管及大血管并发症的发生[1-2]. 有研究发现,与非糖尿病人群相比,糖尿病患者发生冠心病的风险可增加2 ～4倍[3]. 在补体系统激活过程中,经典途径的启动因子补体1q (C1q)在调控机体炎症反应等方面也有重要作用. C1q的激活会加剧许多慢性炎症性疾病,包括冠心病[4]. 目前,C1q的临床相关研究日益丰富,但其在T2DM并发冠心病发生发展过程中的作用尚不明确. 本研究通过检测并比较T2DM合并冠心病患者血浆C1q及相关生化指标水平,探讨C1q与T2DM合并冠心病的关系及其可能的临床意义.

目的:探讨胰高血糖素样肽1(GLP-1)类似物利拉鲁肽(Lir)对高同型半胱氨酸血症(Hhcy)大鼠海马损伤的保护作用及其机制.方法:40只SD大鼠随机分为对照(Ctrl)组、模型(Hhcy)组、Lir低剂量(12.5μg·kg-1·h-1)组、Lir中剂量(25.0μg·kg-1·h-1)组和Lir高剂量(37.5μg·kg-1·h-1)组,采用Western blot法检测大鼠海马组织内丝裂原活化蛋白激酶(MAPK)信号通路中p38、JNK和ERK1/2的蛋白表达及活性依赖的磷酸化水平,同时采用Western blot和免疫组织化学法检测内质网应激标志蛋白免疫球蛋白重链结合蛋白(BIP)和C/EBP同源蛋白(CHOP)的表达水平;采用酶标法检测超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;酶联免疫吸附法检测炎症因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平.结果:Hhcy可明显上调p-p38、BIP和CHOP的蛋白表达量,降低SOD和GSH的活性,升高MDA含量及IL-1β、IL-6和TNF-α水平;腹腔注射Lir可浓度依赖性地改善Hhcy引起的上述内质网应激和炎症反应,并伴有p38 MAPK通路的抑制.结论:Lir可改善Hhcy诱导的大鼠海马组织氧化应激和炎症损伤,其机制可能与抑制p38 MAPK信号通路的过度激活有关.

Objective To investigate the regulatory effects of c-Jun N-terminal kinase(JNK) signaling pathway on islet β-cell apoptosis induced by obesity.Methods Male SD rats were selected to establish obese models by feeding high fat diet.Rats in normal control group(n=10)and obese model group(n=10)were picked out for testing.The levels of fasting plasma glucose(FPG),free fatty acids (FFA),serum fasting insulin(FINS)were measured and insulin resistance index(HOMA-IR)was calculated.The pathological changes of pancreatic tissues were observed. FINS in pancreatic tissues, apoptotic index in pancreatic cells and tumor necrosis factor(TNF)-α,interleukin(IL)-1β,phosphorylated c-jun N-terminal kinase(p-JNK),B cell lymphoma/lewkmia-2(Bcl-2)and Bcl-2 relaed X protein in pancreatic tissves Bax in pancreatic tissues were tested.Results The structure of pancreatic acinus were damaged,and there were obvious lipid deposition inpancreatic tissues. Compared with normal control group,the levels of FPG,FFA,FINS,HOMA-IR,apoptotic index of β cells,TNF-α,IL-1β,p-JNK and Bax significantly increased and the level of Bcl-2 profoundly decreased in obese model group(P <0.05). Conclusion JNK signaling pathway was activated in the obese rats,and then played a positive role in the apoptosis of pancreatic β-cells.

Objective To investigate changes in the expressions of serum homocysteine (Hcy), folic acid (FA) and vitamin B12 ( VitB12 ) in the patients with diabetic neurogenic bladder ( DNB) and the relationship with bladder function .Methods Chosen for the study were 241 patients of type 2 diabetes mellitus ( T2DM) admitted into the hospital for treatment from January 2013 to December 2015, of whom 94 were DNB patients (the DNB group) and 147 were non-DNB patients (the non-DNB group).Serum Hcy, FA and VitB12 were detected in the patients of the 2 groups, and the correlation between serum Hcy , FA and VitB12 and bladder function of the DNB patients was analyzed in the study .Results The levels of serum Hcy [(24.00 ±8.20)μmol/L], fasting plasma glucose (FPG) [(9.17 ±2.00) mmol/L] and triglyceride (TG) [(2.24 ±0.75) mmol/L] in the patients of the DNB group were significantly higher than those of the non-DNB group [(11.66 ±4.47) μmol/L, (7.40 ±1.98) mmol/L and (1.62 ±0.50) mmol/L] (P<0.05).The&nbsp;levels of folic acid (FA) (15.01 ±4.45) μg/L, VitB12(246.92 ±84.00)μg/L and fasting insulin (Fins) (0.81 ±0.26)mU/L in the patients of the DNB group were significantly lower than those of the non-DNB group [(23.46 ±5.72) μg/L,(340.51 ±109.84)μg/L and(0.63 ±0.31)mU/L] (P <0.05).The bladder functional urethral length (FUL) and maximum urethral pressure (PMU) in the patients of the DNB group were significantly higher than those of the non-DNB group (P <0.05).The level of bladder compliance (BC) for the patients of the DNB group was obviously lower than that of the patients in the non DNB group (P <0.05).In the pa-tients of the DNB group, the levels of FA and VitB12 were positively correlated with BC (P <0.05), the level of Hcy was negatively correlated with the level of BC , PMU was negatively correlated with FA and VitB 12 , and PMU was positively correlated with Hcy ( P <0.05).Conclusion The expression levels of Hcy, FA and VitB12 changed considerably, in the patients of the DNB group, and they were closely correlated with the bladder function of the patients .

Objective To investigate the effects of obesity on islet β-cell apoptosis and the possible mechanisms.Methods Obese models were established in male SD rats by high fat diet.The rats in the obese model group(n=10)and the normal con-trol group(n=10)were selected for detecting fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),free fatty acids(FFA),fasting insulin(FIns)and calculating insulin resistance index(HOMA-IR).The pathological changes of the pancre-atic tissues were observed by hematoxylin-eosin(HE)staining and the apoptotic islet β cells were measured by TdT-mediated dUTP-biotin nick end labeling(TUNEL)method.Cytochrome C(Cyt C)in mitochondria,cytoplasm and cleaved cysteine aspar-tate-specific protease-3(Caspase-3)in islet β cells were determined by Western blotting.Results The levels of FBG,TC,TG, FFA,FIns,HOMA-IR,apoptotic index and Cyt C in cytoplasm and cleaved Caspase-3 were significantly increased and the level of Cyt C in mitochondria was profoundly decreased in the obese model group as compared with the normal control group(all P<0.05).In the rats of the obese model group,the structure of pancreatic tissues was damaged,and there was obvious steato-sis.Conclusion Obesity can increase the apoptotic level of islet β cells by activation of mitochondrial apoptotic pathway.

目前,糖尿病在全世界呈爆发式流行,中国成年人群的糖尿病总体患病率约为11.6%[1].糖尿病周围神经病变(DPN)是糖尿病患者最常见的慢性并发症之一和最主要的致残因素,有研究显示,30岁以上2型糖尿病(T2DM)患者DPN的发生率为61.8%[2],患者易因为DPN导致的保护性感觉迟钝或丧失发生足部溃疡和感染,甚至导致截肢[3].临床上多采用α-硫辛酸和甲钴胺治疗DPN,取得了一定的疗效.前列地尔的主要成分是前列腺素E1,以脂微球为药物载体,具有靶向分布到受损血管发挥扩张血管和抗血小板聚集作用.我们通过神经病变主觉症状问卷(TSS)评分及各项电生理指标,评价前列地尔与α-硫辛酸和甲钴胺联合应用治疗T2DM患者DPN的疗效,旨在探讨三药联合治疗的作用机制,以期寻求更为安全有效的改善糖尿病周围神经损伤的治疗方法.

Objective To compare the accordant rate of total light chains and free light chains in serum and urine of mutiple myeloma(MM)patients,and to discuss its clinical significance.Methods 128 MMpatients were included and detected for free and total light chains of serum and urine.Calculate and compare the accordant rates of free and total light chains in serum and urine respectively.Results Among the 128 MM patients,72 cases of serum free light chains(sFLCs)and serum total light chains (sTLCs)were accordant,the accordant rate was 56.25%.119 cases of urinary free light chains(uFLCs) and total light chains(uTLCs)were accordant,the accordant rate was 92.97%.There was a significant difference between the two groups.Conclusion In MM patients,the accordant rate of the TLC and FLC in serum is not high,nevertheless the accordant rate of the TLC and FLC in urine is very high.Therefore, the detection of uFLCs can be substituted by uTLCs in primary hospitals.

目的 评估长期使用内源性大麻素(AEA)对成年鼠的体重、附睾脂肪组织和代谢相关参数的影响.方法 雄性鼠从哺乳期全程口服豆油乳化的AEA 20μg/g.断奶后每10d对其摄食和体重进行记录.成年后行葡萄糖-胰岛素耐受测试.随后,处死小鼠得到其附睾脂肪,并对其血浆中的胰岛素、瘦素、非酯化脂肪酸、甘油三酯和胆固醇进行测定.结果 哺乳期AEA处理组的小鼠在成年后表现出比较对照组较高的摄食量、较重的体重和较多的附睾脂肪.对附睾脂肪组织的CBR1蛋白的测定中,AEA处理组比对照组小鼠增高约1.5倍.AEA处理组小鼠外周循环中有较高的葡萄糖、胰岛素、瘦素、甘油三酯、胆固醇和非酯化脂肪酸.且AEA处理组小鼠表现出一系列显著的胰岛素抵抗的指标.结论 在小鼠哺乳期使用AEA处理后其成年小鼠的体重、脂肪积累和对代谢产生干扰.

目的:观察前列地尔、硫辛酸和西洛他唑3药联合使用对糖尿病周围神经病变(DPN)的疗效.方法:DPN患者76例,随机分为对照组和治疗组各38例,在糖尿病基础治疗基础上,对照组给予前列地尔和硫辛酸治疗,治疗组给予前列地尔、硫辛酸和西洛他唑3药联用.于治疗前和治疗4周后,检测并分析2组运动神经传导速度(MCV)、感觉神经传导速度(SCV)、运动神经复合肌动作电位(CMAP)波幅、CMAP潜伏期和感觉神经动作电位(SNAP)波幅的变化和神经病变主觉症状问卷(TSS)评分.结果:治疗前,2组TSS评分、神经传导速度、CMAP波幅、CMAP潜伏期和SNAP波幅无统计学差异(P＞0.05);治疗后,2组TSS评分和CMAP潜伏期均低于治疗前,且治疗组低于对照组(P＜0.01);2组MCV、CMAP波幅、SNAP波幅和SCV均较治疗前提高(P＜0.01),且治疗组优于对照组(P＜0.05).结论:前列地尔、硫辛酸和西洛他唑3药联用治疗DPN疗效好于前列地尔、硫辛酸2药联用.

目的 研究硫化氢(Hydrogen sulfide,H2S)对2型糖尿病大鼠肝脏胰岛素抵抗的影响.方法 取雄性SD大鼠,采用高糖高脂饮食喂养和腹腔注射小剂量STZ的方法制作大鼠2型糖尿病模型,将成模后大鼠随机分为糖尿病组(DM组)、糖尿病+NaHS(H2S供体)组(DM+NaHS组)、糖尿病+炔丙基甘氨酸(PAG,CSE的抑制剂)组(DM+ PAG组),另设对照组,各15只.每日在固定的时间腹腔注射受试制剂,DM+ NaHS组注射NaHS 56 μmol/(kg·d),DM+PAG组给予PAG 50 mg/(kg·d),对照组和DM组注射相同体积的生理盐水,连续给药2周后处死大鼠.分别检测各组空腹血糖、血浆胰岛素水平、肝脏组织中H2S水平,苏木精-伊红染色观察各组肝脏组织病理学变化;免疫组化法检测胰岛素受体底物-2(IRS-2)的表达;Western blot和RT-PCR检测胱硫醚-r裂解酶(CSE)、胰岛素受体(InsR)和IRS-2的表达.结果 与对照组相比,DM组空腹血糖水平升高、胰岛素水平明显下降,CSE表达明显升高,InsR、IRS-2表达明显降低(均P＜0.05),肝小叶结构破坏,脂肪变性明显,有炎症细胞浸润;与DM组比较,DM+ NaHS组空腹血糖水平明显升高(P＜0.05),胰岛素水平、CSE、InsR、IRS-2表达明显降低(均P＜0.05),肝组织病变更明显;与DM组比较,DM+ PAG组空腹血糖水平、CSE表达明显降低(均P＜0.05),而胰岛素水平、InsR、IRS-2表达明显升高(均P＜0.05),肝组织病变有所减轻.结论 H2S可通过下调2型糖尿病大鼠肝细胞InsR和IRS-2的表达水平,促进胰岛素抵抗;PAG可通过上调2型糖尿病大鼠肝细胞InsR和IRS-2的表达水平,改善胰岛素抵抗.

目的 观察贝美前列素治疗眼球钝挫伤后继发性青光眼的疗效,并探讨其作用机制.方法 回顾性分析2014年9月-2016年5月间收治住院11例患者11只眼球钝挫伤后继发性青光眼,经贝美前列素联合其他治疗后眼压控制情况.结果 11例患者中9例眼压降至正常,眼压降幅1.995～ 5.985 kPa,平均4.243 kPa.2例经药物及常规治疗后眼压仍不能稳定于正常范围内,其中1例行睫状体光凝术后眼压降至正常范围,1例行后段玻璃体切割术后联合用药,眼压降至正常范围.结论 贝美前列素能显著降低眼球钝挫伤后继发性青光眼患者的眼压,且能在其他抗青光眼药物降压效果不佳时发挥良好的降眼压作用.

Objective To explore the influence of the cannabinoid receptor antagonist rimonabant on anandamide( AEA) and glucose metabolism of diabetic rats.Methods Total of 40 SPF male rats were divided into an experimental group and a control group by random number table method ,20 each.Both groups were fed with high sugar and high fat diet and intraperitoneal injection of streptozocin ( 50 mg/kg ) for 3 weeks.The experimental group was treated with rimonabant(10 mg/kg) and was continued with high-sugar high-fat diet for three weeks,while the control group was given 0.9%NaCl injection.The AEA,serum insu-lin,blood sugar and glycated serum level were tested at before the start of the experiment (T1),at the week-end of 3 weeks ( T2 ) ,and 6 weeks ( T3 ) .Results In the experimental group,the level of Serum AEA was increased and then decreased at 3 weeks and 6 weeks,and the level of AEA in the control group was gradually increased[experimental group:(0.69 ±0.12) mg/L,(0.32 ±0.05) mg/L vs (0.43 ±0.06) mg/L;con-trol group:(0.72 ±0.17) mg/L,(0.73 ±0.23) mg/L vs (0.45 ±0.08) mg/L].There was significant difference between groups and different time points ( P <0.05 ) .There was no significant difference in the interaction effect between the two groups(P>0.05).In the experimental group,the level of serum blood glu-cose and glycosylated hemoglobin was increased and then decreased at 3 weeks and 6 weeks [ ( 16.2 ± 3.6) mmol/L,(11.0 ±2.7) mmol/L vs (6.8 ±1.0) mmol/L; (12.7 ±2.7)%,(7.8 ±2.6)% vs (5.6 ±1.2)%],and the level of serum blood glucose and glycosylated hemoglobin in the control group was gradually increased[(16.8 ±2.7) mmol/L,(17.0 ±3.3) mmol/L vs (6.7 ±0.9) mmol/L ,(14.0 ± 2.2)%,(15.0 ±2.8)% vs (5.6 ±1.3)%.In the experimental group ,the level of serum insulin was decreased and increased at 3 weeks and 6 weeks [(6.7 ±1.9) U/L,(9.4 ±1.3) U/L vs (20.4 ± 4.7) U/L,and the level of serum insulin in the control group was gradually decreased[(6.0 ±1.2) U/L, (5.7 ±1.2) U/L vs (21.3 ±4.2) U/L].There were significant differences between the two groups in serum blood glucose,glycosylated hemoglobin and serum insulin(P<0.05).There was no significant differ-ence in the interaction effect between the two groups in serum blood glucose , glycosylated hemoglobin and serum insulin(P>0.05).Conclusion Cannabinoid receptor antagonist rimonabant can reduce the level of AEA in rats,reduce the blood sugar and improve insulin resistance.

Objective To investigate the effects of hydrogen sulfide on insulin sensitivity and lipid metabolism in type 2 diabetic rat model.Methods The type 2 diabetes mellitus (T2DM) rat model was established by high-fat and high-glucose diet and low-dose intraperitoneal injection of stretopzin (STZ).The model rats were randomly divided into diabetes(DM) group (n =15),DM + NaHS group (n =15),and DM + DL-propargylglycine(PAG) group (n =15),and the normal control group was set up (n =15).The animals in DM + NaHS group were given NaHS [56 μmol/(kg· d)],those in DM +PAG group given PAG [50 mg/(kg·d)],and those in control and DM groups given the same volume of saline for 2 weeks.Behavioral characteristics were observed in all groups.The serum levels of fasting blood glucose (FBG) and insulin (FIns),triglycerides (TG),total cholesterol (TC),free fatty acid (FFA) and hydrogen sulfide (H2S) concentrations in the diabetic models were measured to calculate HOMA-IR and ISI.H2S concentrations in pancreatic tissue were measured.The expression of insulin was detected by immunohistochemistry in pancreatic tissue.Results The typical symptoms of diabetes were observed in T2DM rats.As compared with control group,plasma FBG [(18.22 ± 3.99) mmol/L],TG [(1.54 ±0.16) mmol/L],TC [(3.27 ± 0.38) mmol/L],FFA [(504.68 ± 37.70) μmol/L] levels and HOMA-IR were significantly increased in DM group; FIns [(41.79 ±3.43) mU/L] and ISI (-6.57 ±0.37) were significantly decreased,H2S concentration [(96.98 ± 19.44) μmol/L] in pancreatic tissue was significantly increased,and the areas of insulin-expression positive cells and positive rate of insulin staining cells were significantly decreased (P ＜ 0.05).As compared with DM group,plasma FBG [(25.42±0.21) mmol/L],TG [(2.40 ±0.21) mmol/L],TC [(4.80 ±0.16) mmol/L],FFA [(633.96 ±25.64) μmol/L] levels and HOMA-IR were significantly increased in DM + NaHS group; FIns [(29.36 ±2.65) mU/L] and ISI (-6.58 ±0.27) were significantly decreased,H2S concentration in pancreatic tissue [(134.50 ± 12.70) μmol/L] was significantly increased,and the areas of insulin-expression positive cells and positive rate of insulin staining cells were significantly decreased (P ＜ 0.05).As compared with DM group,plasma FBG [(10.83 ± 1.10) mmol/L],TG [(1.30 ±0.12) mmol/L],TC [(2.79 ±0.33) mmol/L],FFA [(383.39 ±69.00) μmol/L] levels and HOMA-IR were significantly decreased in DM + PAG group,FIns [(51.58 ± 1.49) mU/L] and ISI (-6.32 ± 0.11) were significantly increased,H2S concentration in pancreas tissue [(71.48 ± 10.94) μmol/L] was significantly decreased,and the areas of insulin-expression positive cells and positive rate of insulin staining cells were significantly increased (P ＜ 0.05).Conclusion H2S may be involved in the development of T2DM through influencing the insulin sensitivity and lipid metabolism.

目的:评价西格列汀联合地特胰岛素治疗老年2型糖尿病的疗效及安全性.方法:将88例口服降糖药控制不佳的老年2型糖尿病患者随机分成2组,观察组(西格列汀联合地特胰岛素组)和对照组(瑞格列奈联合地特胰岛素组)各44例;观察12周,比较治疗前后2组患者的空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹C肽(FC-P)、体重指数(BMI)、胰岛素用量及低血糖发生情况.结果:治疗后2组FPG、2hPG、HbA1c均较治疗前显著降低(P＜0.05),观察组FC-P较治疗前显著增高(P＜0.05),BMI较治疗前略有下降,但无显著性差异(P＞0.05),对照组FC-P及BMI较治疗前均无显著性差异(P＞0.05);组间比较两组治疗后FPG、2hPG、HbA1c无显著性差异(P＞0.05),观察组FC-P较对照组显著增高(P＜0.05),胰岛素用量显著减少(P＜0.05),BMI显著下降(P＜0.05).观察组低血糖发生率较对照组显著降低(P＜0.05).结论:西格列汀联合地特胰岛素治疗老年2型糖尿病疗效确切,且可改善胰岛3细胞功能,安全性好.

目的:探讨硫化氢(H2S)合成酶抑制剂DL-炔丙基甘氨酸(PAG)对其2型糖尿病(T2DM)大鼠胰岛β细胞功能和凋亡相关蛋白的影响.方法:采用高糖高脂饮食喂养和腹腔注射小剂量STZ的方法建立大鼠T2DM模型,将成模大鼠按随机数字表法随机分为糖尿病组(DM组),糖尿病+DL-炔丙基甘氨酸组(DM+ PAG组),另设正常对照组,各15只.每日固定时间腹腔注射受试制剂,DM+ PAG组给予PAG[50 mg/(kg· d)],对照组和DM组给予相同体积的生理盐水,连续给药2周.投药结束后,检测各组大鼠空腹血糖(FBG)、血浆胰岛素(FIns)水平,胰腺组织中H2S水平,免疫组化法检测分析胰腺组织胰岛素、Caspase-3、Bax和Bcl-2的表达情况,并计算胰腺组织相对β细胞数量和平均β细胞面积.结果:与对照组相比,DM组大鼠血浆FIns降低,FBG升高,胰腺组织H2S浓度水平升高;胰腺组织胰岛素阳性颗粒减少,Caspase-3、Bax表达增强,Bcl-2的表达减弱,Bc1-2/pax比值降低;相对β细胞数量和平均β细胞面积均明显减小;经PAG处理后,大鼠血浆FIns明显升高,FBG降低,胰腺组织H2S浓度明显降低;胰腺组织胰岛素阳性颗粒明显增多,Caspase-3、Bax表达减弱,Bcl-2的表达增强,Bc1-2/Bax比值升高;相对β细胞数量和平均β细胞面积增加.结论:内源性H2S通过调节胰岛β细胞凋亡相关蛋白表达,促进胰岛β细胞的凋亡,减少2型糖尿病大鼠胰岛β细胞的相对数量,从而减少胰岛素的分泌;而PAG能减少胰岛β细胞凋亡,增加2型糖尿病大鼠胰岛β细胞的相对数量,增加胰岛素的分泌,达到控制血糖的目的.

Objective To observe the changes of thyroid function in L-carnitine treatment of type 2 diabetes mellitus(DM)with chronic heart failure(CHF)patients.Methods 64 cases DMpatients with CHF were randomly divided into L-carnitine group(32 cases)and control group(32 cases).Both groups underwent conventional anti-heart failure treatments.Besides,the L-carnitine group were treated with 2 g of L-carnitine in intravenous pump twice a day in a total amount of 14 d.Indicators such as left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),cardiac output(CO),N-terminal pro-brain natriuretic peptide(NT-pro-BNP),triiod-thyronine(T3 ),free triiodthyronine(FT3 ),free thyrox-ine(FT4 )and thyroid stimulating hormone(TSH)were detected 14 days after medical treatments,and each indicator was compared with the one before the treatments and the corresponding control group data re-spectively.Results L-carnitine improved heart function in patients with heart failure,T3 ,FT3 level com-pared with before treatment and the control group had significant increased difference(P <0.05),showing no obvious adverse reactions,and glucose(GLU),triglyceride(TG),cholesterol(CHO)had sharp tenden-cies of declining compared to those before treatments.Conclusion L-carnitine have a significant effect on the treatments of type 2 diabetes mellitus with chronic heart failure.It can improve thyroid function and have no significant adverse reactions.

目的 观察二肽基肽酶-4抑制剂(DPP-4抑制剂)西格列汀对2型糖尿病合并早期糖尿病肾病(DN)患者肾功能的影响.方法 将74例口服降糖药物(除外DPP4抑制剂)治疗的2型糖尿病合并早期糖尿病肾病患者,随机分为西格列汀组(36例)和对照组(38例),西格列汀组原治疗方案加用西格列汀;对照组按原治疗方案增加药物剂量或联合除DPP4抑制剂外降糖药物治疗,两组控制目标均为糖化血红蛋白(HbA1c) ＜7％.结果 治疗12周后,两组胱抑素C(CysC)、β2微球蛋白(β2-MG)水平较治疗前显著降低(P＜0.05),但西格列汀组下降更加明显,两组间比较差异有统计学意义(P＜0.05).结论 西格列汀能显著改善早期糖尿病肾病的肾脏损害程度.