糖尿病性肌病的超微病理结构及可能机理

目的 研究 2型糖尿病性肌病患者肌肉的超微结构。 方法 随机收集 10例 2型糖尿病性肌病患者的腓肠肌活检标本 ,利用透射电镜进行观察。 结果 可见骨骼肌细胞通透性肿胀 ,肌膜下区水肿 ,肌纤维明显溶解 ,线粒体中有巨大的髓磷体及钙颗粒缺乏 ,异常蛋白质沉着于细胞内外 ,肌细胞萎缩及类凋亡。清晰可见微血管内皮细胞功能不良的形态标志 ,偶见坏死及“无细胞性微血管”形成 ,血管基底膜增厚和神经纤维的明显受损。 结论 2型糖尿病性肌病患者腓肠肌组织中的各类细胞及基质均是高血糖毒性所攻击的靶子 。

糖尿病合并肌痛一例报道

目的 本文报道1例老年男性T2DM患者血糖控制不佳,无明显诱因出现左下肢肌肉疼痛,血肌酸激酶(CK)升高,核磁共振(MRI)提示左股二头肌短头、比目鱼肌异常信号,增强扫描后可见均匀强化,诊断为糖尿病肌病。经休息、胰岛素降糖等治疗,患者疼痛好转,CK下降,MRI肌肉异常信号消失。糖尿病肌病是较少见糖尿病并发症,常出现于血糖控制不良患者,临床上极易被忽视,需早期诊断治疗,避免发展至坏死性筋膜炎、脓性肌炎等严重并发症。

糖尿病并发症的研究进展

糖尿病是严重危害人们健康的常见病，易并发多种并发症，已成为糖尿病患者致残、致死的重要原因。本文根据该专栏征集的7篇论著涉及的研究内容，简要综述了糖尿病肾病、糖尿病视网膜病变、糖尿病骨骼肌病变、糖尿病勃起功能障碍和糖尿病非酒精性脂肪肝病的研究进展及其共同相关的发病机制，并提出了糖尿病及其并发症的防治策略，为深入研究糖尿病并发症及其临床防治和新药研发提供启示。

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus （STZ） and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ （45 mg/kg） and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase Lnitroarginine methylester （L-NAME） （40 mg/kg） for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase （A1Ph）, dipeptidyl peptidase IV （DPP IV）, and endothelial NO synthase/NADPH-diaphorase （NOS） and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent A1Ph and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of A1Ph, DPP and NOS by 49.50%,74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. Concluding： both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.

Pathology of diabetic myocardiac microangiopathy

Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity fi＇om those in controls. Nor was there difference in number ofmyofibers or diameters of myoeardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group（P〈0.0 l）,and the capillary basement membrane in the former was significantly thicker than in the latter（P〈0.01）.Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.

Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy

Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneal y for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase （TDT）-mediated DNA nick-end labeling （TUNEL） and immunohistochemistry. Ginsenoside Rg1 was as-sociated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants （superoxide dismutase, catalase, and glutathione peroxidase） were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 （CASP3） and increased levels of B-cell lymphoma-extra-large （Bcl-xL） in the diabetic myocardium. Ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.

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.

Study on the Protective Effect of Shengmai San(生脉散) on the Myocardium in the Type 2 Diabetic Cardiomyopathy Model Rat

Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin(50 mg/kg).And these rat models were randomly divided into three groups:a normal group(n=12,one of them died),a model group(n=15) and a Shengmai San group(treatment group,n=15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling,and the blood glucose,cholesterol and triglyceride levels were determined;the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test;the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit;the damage extent of the myocardial sub-cellular structures was observed by electron microscopy;the expression levels of cardiac TSP-1(Thrombospondin-1),TGF-β1(Transforming Growth Ffactor-β) and TRB-3(Tribbles homolog 3) proteins were detected by immunohistochemical method;the expression levels of cardiac TSP-1,A-TGF-β1 and L-TGF-β1 proteins were detected by Western blotting;and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR.Results:Compared with the control group,the blood glucose,cholesterol,triglycerides levels in both the model groups and the Shengmai San group were significantly decreased;the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group;the myocardial sub-cellular structure was injured to a lesser extent;the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and TSP-1,A-TGF-β1,L-TGF-β1 and chymase were decreased,and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group(the latter was better),.Conclusion:Shengmai San can inhibit myocardial fibrosis in the rat of diabetic cardiomyopathy,and significantly delay the formation of diabetic cardiomyopathy in hyperglycemia rats through multiple pathways.