Objective To study the relationship of angiotensin Ⅱ type 1 receptor (AT1R) autoantibody (AT1-AA) and renal cell apoptosis induced by caspase-12 in diabetic nephropathy (DN)rats.Methods High-sucrose and high-fat diet and intraperitoneal injection of streptozotocin (35 mg/kg) were utilized to establish DN rat model.Serum AT1-AA was detected by enzyme-linked immunosorbent assay (ELISA) and renal cell apoptosis was detected by TUNEL staining.Furthermore,the mRNA levels of the endoplasmic reticulum stress (ERS) chaperone protein glucose regulated protein 78 (GRP78) and ERS-associated apoptosis protein caspase-12 were measured by real-time quantitative PCR.Additionally,the levels of GRP78 and caspase-12 protein were measured by Western blotting.Results The renal cell apoptosis rate in DN group was increased significantly (P ＜ 0.01),and the renal cells apoptosis rate in AT1-AA positive DN group was higher than that in AT1-AA negative DN group [(20.05±1.71)％ vs (13.24±4.93)％,P ＜ 0.01].The mRNA expressions of GRP78 and caspase-12 in DN group,in comparison to NC group,were increased significantly (P ＜ 0.01),as well as the proteins (P ＜ 0.01).And the expression of these mRNA and proteins had significant increment in AT1-AA positive DN rats when compared with AT1-AA negative DN rats (P ＜ 0.05).Conclusions AT1-AA can induce ERS in the renal tissue of DN rats,and promote renal cell apoptosis likely via the modulation of caspase-12 signaling pathway.

Objective To investigate the protective effects of aerobic exercise and miR-222 expression in myocardium of diabetic mice. Methods C57BL/ 6 mice were divided into 4 groups: normal non-exercise group (SC), normal exercise group(EC), non-exercise diabetic group(SD), and exercise diabetic group(ED). After the diabetic model was established successfully, EC and ED underwent a swimming training for 5 weeks. By the end of the experiment, light microscope was used to observe the pathological changes of heart, RT-PCR for myocardial miR-222 expression, and Western blot for phosphatase and tensin homolog deleted on chromosome ten ( PTEN ), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) protein expressions in myocardial tissue. Results (1) Under the light microscope, the diabetic mice had a significant change in myocardial structure, with great disorder in the cell arrangement. After exercise intervention, the lesion was alleviated. (2) MiR-222 expression was increased in the myocardium of normal mice and DM mice after exercise (all P<0. 05); (3) Compared with SC group, PTEN expression was increased and PI3K/ Akt expressions were inhibited in myocardium of diabetic mice(all P <0. 05). After exercise intervention, the expression of PTEN reduced( P < 0. 05) and PI3K/ Akt pathway was reactivated in myocardium of diabetic mice (all P<0. 05). Conclusion Exercise intervention may protect the myocardium under high glucose via inducing miR-222 and activating PI3K/ Akt signaling pathway.

MicroRNAs (miRNAs) are a class of endogenous;non-coding small RNA molecules;which can degradate target mRNA;or negatively regulate the expression of the corresponding target genes in the post transcriptional level through inhibiting target gene translation;inducing degradation and so on.MiRNAs exert important parts in the process of metabolism;cell growth;and development.MicroRNA 222 (miR-222) is an important member of microRNAs;which plays an important role in cell proliferation;differentiation;apoptosis and the development of a variety of biological tissues.Recent studies found that miR-222 could mediate a variety of physiological and pathological processes;and significantly influence the development of cardiovascular disease.MiR-222 has an important role in inflammatory response and apoptosis.Here;we reviewed the relationship between miR-222 and cardiovascular disease.

Objective To explore the relationship of autoantibodies against G protein coupled angiotensin Ⅱ-1 receptor (AT1 R),α1-adrenergic and β1-adrenergic receptors (α1 R and β1 R) with thyrotoxicosis heart disease (THD).Methods The epitopes of the second extracellular loop ofAT1 R (165-191),α1 R (192-218),and β1 R(197-222) were synthesized for screening autoantibodies from 277 participants by ELISA.237 patients with thyrotoxicosis were subdivided into thyrotoxicosis treatment group (n =148) and thyrotoxicosis recovery group (n =89),or into THD group (n =46) and simple hyperthyroidism group (n =191).40 healthy subjects were served as control group.Results (1) The positive rates of autoantibodies against AT1 R,α1 R and β1 R in thyrotoxicosis patients were higher than those in the control subjects (31.6％ vs 12.5％,27.8％ vs 10.0％,and 23.6％ vs 7.5％,all P＜0.05).The positive rates of the three autoantibodies in the patients with Graves' disease were higher compared with thyrotoxicosis caused by other reasons (36.3％ vs 19.7％,32.2％ vs 16.7％,and 28.1％ vs 12.1％,all P＜0.05).(2) In thyrotoxicosis treatment group,the positive rates of autoantibodies against AT1 R and α1 R were higher than those in the hyperthyroidism recovery group (40.5％ vs 16.9％ and 33.1％ vs 19.1％,both P＜0.05).(3) The incidence of autoantibodies against AT1 R and α1 R in THD were significantly higher compared with simple hyperthyroidism (52.2％ vs 26.7％ and 43.5％ vs 24.1％,both P＜0.05).Conclusions Autoantibodies against AT1 R,α1 R,and β1 R may play important roles in the pathogenesis of hyperthyroidism,which may be involved in the progression of THD.

AIM: To study the protective effect of aerobic exercise on cardiac dysfunction in mice and its mechanism, and to provide theoretical and practical basis for the exercise therapy of diabetic cardiac dysfunction .METH-ODS:The mice were divided into normal control non-exercise (NNC) group, normal control exercise (ENC) group, dia-betic non-exercise (NDM) group and diabetic exercise (EDM) group.At the end of the experiment , the cardiac function was evaluated by echocardiography .The pathological changes of the myocardial tissues and the development of fibrosis were observed.The mRNA expression of ANP, and the protein levels of PI3K (p110α) and Akt were determined.RESULTS:The decrease in cardiac function of diabetic mice was observed , and the cardiac function recovered after exercise interven-tion (P<0.05).Under light microscope with HE and Masson staining , the myocardial structure in NDM group was in ex-treme disorder , cell arrangement was not neat , and the degree of fibrosis increased , but the myocardial damage was im-proved in ENC group .Compared with NNC group , the mRNA expression of ANP in the myocardium of diabetic mice was up-regulated (P<0.05).The protein levels of PI3K (p110α) and Akt were decreased (P<0.05), and the cascade was inactivated.Compared with NDM group , the mRNA expression of ANP was down-regulated and the protein levels of PI 3K (p110α) and Akt were up-regulated in EDM group (P<0.05).CONCLUSION:Diabetes results in myocardial damage in mice, and reduces cardiac function .Exercise intervention alleviates the heart dysfunction induced by high glucose via activating PI3K( p110α)/Akt signaling pathway to protect the structure and function of the myocardium .

Objective To explore the role of the autoantibodies against angiotensin Ⅱtype 1 receptor(AT1-receptor) and ?1-adrenergic receptor(?1-receptor)in the development of chronic glomerulonephritis(CGN) with renal failure.Methods The epitopes of the second extracellular loop of AT1 receptor(165-191),?1 receptor(192-21),M2 receptor(169-191) were synthesized and used respectively to screen sera autoantibodies from patients with chronic renal failure(n=66),hypertension without renal failure(n=58) and healthy blood donors(n=40,control) by ELISA.Results In patients of chronic glomerulonephritis with renal failure,the positive rates of the autoantibodies against AT1-receptor and ?1-receptor were 56.1% and 53.0% respectively.The positive rates were all higher than those in patients of the hypertension without renal failure(the positive rates were 15.5% and 12.1%,respectively) and in the healthy donors(10% and 12.5%,respectively)(P

Objective To make a status survey on type2 diabetic patients with metabolic Syndrome in middle-aged inhabitants.Methods 338 inpatients with type 2 DM including 179 male and 159 female,aged 46?5 years,with complete records in the computer database.Results The prevalent rates of the complications in group of 40～yrs type2 diabetic patients were 17.8% combined with coronary atherosclerotic heart disease,50.9% with hypertension,18.1% with left ventricular dilatation,53.6% with hypertriglyceridemia,46.2% with lower HDL,54.7% with obesity and 38.8% with metabolic Syndrome,respectively.These prevalent rates in the 40-year-old group were all lower than those in groups above 60 years,and the rates was higher in patients whose BMI was above 25(kg/m2).Conclusion There was high prevalence in type 2 diabetic patients with metabolic Syndrome,and was related with the age and obesity.Obesity was an independent risk factor for MS.

Objective To investigate the role of AT1 receptor autoantibody (AT1-AA) in the inhibitory action of irbesartan on endoplasmic reticulum stress (ERS)-related apoptotic signals in rat kidney with diabetic nephropathy (DN).Methods DN model rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin,and the serum level of AT1-AA was detected by ELISA.These DN rats with positive or negative AT1-AA were divided into DN group and irbesartan treated group.After 4 weeks of irbesartan treatment,TUNEL staining was used to detect renal cell apoptosis.The protein and mRNA expressions of ERS chaperone protein glucose-regulated protein 78 (GRP78) and ERS-associated apoptosis proteins were determined by Western blot and RT-PCR.Results Compared with NC group,the apoptosis rate of renal cells in DN group was obviously increased,along with the increased expressions of GRP78,C/EBP homology protein (CHOP),phosphorylated c-Jun N-terminal kinase (JNK),and Caspase12 protein and mRNA (all P＜0.01).The cell apoptosis and protein and mRNA levels of these genes were significantly decreased after irbesartan treatment (all P＜ 0.01),especially in AT1-AA positive DN rats(all P＜0.05).The renal cell apoptosis rate,and protein and mRNA levels of these four genes in AT1-AA positive DN group were much greater than those in AT1-AA negative DN group (all P＜0.05).Conclusions AT1-AA may be involved in ERS-related cell apoptosis in the kidney of DN rats,and play a role in irbesartan-improved renal function via inhibiting ERS-associated CHOP-JNK-Caspase12 apoptotic signals and renal cell apoptosis.

[Summary] Berberine is akind of alkaloids extracted from Chinese herb medicine in cludingphellod endron ,coptis and radix berberidis .In recent years ,the pharmacological effects of berberinewas investigated extensively including anti-infection ,anti-arrhythmia ,protection of ischemic myocardium ,anti-hypertension , anti-tumor ,anti-HIV .And there are increasing reports about its hypoglycemic effect ,but its mechanism remains unclear .Here we summarize the possible mechanism of hypoglycemic effect and clinical efficacy of berberine .

The assay of genotypes of Gln223Arg variant (PCR-RFLP) in 692 subjects of Wuhan Han population with obesity and type 2 diabetes showed that the frequencies of AA and AG genotytpes and A allele were higher in T2DM plus obesity than in isolated T2DM (all P