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Objective To explore the effect of sufentanil postconditioning on the focal cerebral is-chemia reperfusion injury in diabetic rats. Methods An intraperitoneal injection of 50 mg/kg streptozotocin was used to induce diabetes in rats. Meanwhile,the diabetes mellitus model was confirmed by the blood glu-cose level over 16. 7 mmol/L. The diabetes mellitus male SD rats,weighting 250-300 g,were randomly divid-ed into 3 groups:sufentanil postconditioning diabetic group (SP-DM),ischemia reperfusion diabetic group (IR-DM),sham operation diabetic group(sham-DM),with 12 in each group. The non-diabetic rats were randomly divided into 3 groups:sufentanil postconditioning non-diabetic group(SP-NDM), ischemia reperfu-sion non-diabetic group(IR-NDM),sham operation non-diabetic group(sham-NDM),with 12 in each group. All rats in the IR-NDM/DM group and SP-NDM/DM group were exposed to the right middle cerebral artery occlusion for 90 minutes followed by 24 hours reperfusion. The sufentanil 1 μg/kg were injected into the rats in SP-NDM/DM group via tail vein at 5 minutes before reperfusion. Normal saline was injected into the rats in sham-NDM/DM group and IR-NDM/DM group at 5 minutes before reperfusion. At 24 hours after reperfu- sion,the neurological deficit scores( NDS) were assessed,then all the rats were sacrificed. Infarct volume, which was determined by 2,3,5-triph-enyltetrazolium ( TTC) staining,and water content of right hemisphere for brain edema were also measured. Results All rats showed neurological deficit,brain infarction and brain edema after focal cerebral ischemia reperfusion. (1) At 24 hours after reperfusion,the neurological deficit score in IR-DM group(3. 4±0. 4) was significantly higher than that in the IR-NDM group(2. 8± 0. 5) ( t=2. 313,P<0. 05),there was no significant difference in neurological deficit score between the SP-DM group (3. 3±0. 4) and the IR-DM group(t=1. 546,P>0. 05). (2) At 24 hours after reperfusion,the infarct volume in IR-DM group((58. 3±2. 1)%) was significantly higher than that in the IR-NDM group((32. 1±2. 6)%) (t=2. 912, P<0. 05), there was no significant difference in infarct volume between the SP-DM group ((56. 9±2. 1)%) and the IR-DM group(( 58. 3 ± 2. 1)%) ( t=1. 633,P>0. 05). ( 3) At 24 hours after reperfusion,the water content of the right hemisphere in IR-DM group(( 89. 3± 3. 5)%) was significantly higher than that in the IR-NDM group((82. 6±3. 9)%)(t=2. 218,P<0. 05),there was no significant differ-ence in water content of the right hemisphere between the SP-DM group(( 87. 5±3. 4)%) and the IR-DM group(t=1. 730,P>0. 05). Conclusion Sufentanil postconditioning loses neuroprotection against focal cer-ebral ischemia reperfusion injury in diabetic rats.
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Aim To study the anti-diabetic effects of natural product gastrodin ( GSTD ) in KK-Ay mice. Methods C57BL/6J mice were used as normal con-trol, while KK-Ay diabetic mice were divided into five groups, namely the untreated group, GSTD 10 mg· kg-1, 20 mg·kg-1, 50 mg·kg-1 groups, and the metformin ( Met) 200 mg·kg-1 group, respectively, with 10 mice in each group. GSTD and Met were ad-ministered intragastrically for eight weeks. Before ex-periment and once a week during the experiment, the fasting blood glucose ( FBG) levels were determined. During the 7th week of drug treatment, oral glucose tolerance test ( OGTT ) and insulin tolerance test ( ITT) were conducted. Before the end of experiment, 24 h urine samples were collected for the assay of rela-tive parameters. At the end of experiment, blood sam-ples were collected for the assay of glycosylated hemo-globin ( GHb) ; serums were isolated for the determina-tion of insulin concentration and other biochemical in-dexes. After sacrifice, the livers, kidneys, and pan-creases of the mice were harvested for pathological ex-amination; the contents of advanced glycation end product ( AGE) and triglyceride ( TG) in renal tissues were assayed by kits. Results GSTD at all doses sig-nificantly reduced FBG, urine glucose, GHb, serum insulin level, and the insulin resistance index in KK-Ay diabetic mice. In addition, GSTD greatly inhibited body weight gain and improved glucose tolerance and insulin tolerance ( P <0.05 or P <0.01 vs untreated group ) . The pathological examination showed that GSTD significantly increased the glycogen content of liver tissues, reduced islet volume and improved its pathological changes. In addition, the glomerulosclero-sis induced by diabetes was greatly ameliorated by GSTD. Meanwhile, GSTD greatly reduced serum crea-tine ( Scr) , 24 h urine amount, 24 h urine total pro-tein and microalbumin ( mAlb) , as well as renal AGE and TG contents in KK-Ay mice ( P <0.05 or P <0.01 vs untreated group) . The anti-diabetic effect of GSTD at 50 mg·kg-1 was comparable to that of 200 mg·kg-1 of Met. Conclusions When used to treat KK-Ay diabetic mice, GSTD has potent activities in lowering blood glucose, improving insulin resistance and ameliorating diabetic nephropathy. However, the detailed mechanisms of GSTD in modulating glucose metabolism and increasing insulin sensitivity still need further investigation.
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Aim To study the effects of Free Anthra-quinone from Rhubarb (FAR)on myocardial CTGF and collagen expression and interstitial fibrosis in dia-betic rats.Methods The male SD rats were randomly divided into normal group (CON),diabetic cardiomy-opathy group (DCM) and FAR treatment group (FAR).Streptozocin was intraperitoneally injected in-to the animals in the latter 2 groups to induce diabetic rat model.The model was expected to be stable for 2 weeks before the treatment.At the end of the 8th week in treatment,fasting plasma glucose and heart mass in-dex were measured.Masson staining was used to ob-serve the myocardial fibrosis.RT-PCR was used to de-tect the mRNA levels of CTGF,procollagen type Ⅰand collagen type Ⅲ.Immunohistochemical method was used to detect the content of CTGF.ELISA was used to detect the depositions of collagen type I and collagen type Ⅲ. Results Compared with CON group,fasting plasma glucose,heart mass index,the degree of myocardial fibrosis,and the expressions of CTGF,collagen type I and collagen type Ⅲ in left ven-tricular myocardial tissue of DCM group were signifi-cantly increased. However, compared with DCM group,fasting plasma glucose,heart mass index,the degree of myocardial fibrosis,and the expressions of CTGF,collagen type I and collagen type Ⅲ in left ven-tricular myocardial tissue of FAR-treated rats were sig-nificantly decreased.Conclusion FAR retards the process of myocardial fibrosis in diabetic rats by down-regulating the expression of CTGF,reducing the syn-thesis and depositions of collagen type I and collagen type Ⅲ.
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Aim To investigate the alteration of Wnt/β-catenin signaling pathway in early diabetic rat myo-cardium and clarify its role in development of diabetic cardiomyopathy. Methods The diabetes mellitus ( DM) model was prepared by intraperitoneal injection of streptozotocin ( STZ, 60 μg · g-1 ) . The alteration of Wnt/β-catenin signaling pathway was determined by Western blot and immunohistochemistry. HE staining was used to analyze the change of myocardial pathologi-cal structure. Results Cardiac histological analyses revealed that DM induced cardiomyocyte degeneration and necrosis. Myocardial Wnt2, β-catenin and c-Myc were enhanced in 2 wk DM compared with control group while DKK1 showed no significant alteration. Conclusion Wnt/β-catenin signaling pathway is acti-vated in early diabetic myocardial injury. Further re-searches on its role in DM myocardium may find a new therapeutic target for diabetic cardiomyopathy.
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Objective To study the postoperative cognitive dysfunction (POCD) in elderly patients after off‐pump coronary artery bypass grafting (OPCABG)and its risk factors ,and the association between cerebrovascular function assayed by 320 dynamic volume CT and POCD .Methods Two hundred and thirteen elderly patients selected for OPCABG were divided into patients group (n=28) and control group (n=185) .The patients underwent 320 dynamic volume CT to show their cerebrovascular ,neurological and cognitive functions .The patients were assessed on day 14 after operation .The risk factors for POCD and the association between CT perfusion imaging parame‐ters and POCD w ere comparatively analyzed .Results T he incidence of cerebrovascular disease , diabetes mellitus ,CTA‐detected severe cerebrovascular stenosis and abnormal cerebral pufusion was significantly higher in patients group than in control group (P< 0 .01) .Logistic regression analysis showed that cerebrovascular disease history and abnormal cerebral pufusion were the in‐dependent risk factors for POCD (OR= 1 .837 ,95% CI:1 .075 -3 .141 ,P= 0 .026 ;OR= 3 .224 , 95% CI:2 .073-5 .013 ,P=0 .000) .Conclusion Early detection of abnormal cerebrovascular ste‐nosis ,poor cerebral perfusion and maintainence of stable blood glucose play an important role in reducing the incidence of POCD in elderly patients after OPCABG .
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Aim To study the effect of activating Sonic hedgehog( Shh) pathway on the function of endothelial progenitor cells ( EPCs ) in type 1 diabetic mice. Methods EPCs were isolated and cultured by density gradient method from diabetic mice. The effects of Shh N-terminal peptide and agonist SAG on EPCs prolifera-tion were evaluated by using the MTT colorimetric as-say. EPCs migration was measured by Transwell meth-od. EPCs tube formation ability was estimated by Matrigel . EPCs senescence activity was determined by β-galactosidase staining. Results Compared with control mice, the function of EPCs in type 1 diabetic mice was impaired. The proliferation, migration and tube formation of diabetic EPCs could be promoted by Shh peptide and agonist SAG. The senescence of dia-betic EPCs could be decreased by Shh peptide and ag-onist SAG. Conclusion Activating Shh signaling pathway can improve the impared function of diabetic EPCs in type 1 diabetic mice.
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Objective To investigate the additive effects of uncoupling protein 2(UCP2) gene 3′-untranslated region(3′-UTR) 45-base pair insertion/deletion( I/D) variation and peroxisome proliferator activated receptor( PPAR)γ2 gene Pro12Ala variation on type 2 diabetes(T2DM) in Chinese Han popula-tion.Methods The UCP2 gene 3′-UTR I/D variation and PPARγ2 gene Pro12Ala variation were exam-ined by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) in 490 type 2 dia-betes subjects and in 585 control subjects .The additive effects of the two gene mutations were analyzed . Results ⑴The frequency of PPARγ2 gene Pro12Ala variation in type 2 diabetes was not significantly dif-ferent from that in control subjects.(χ2 =0.058, P =0.809).In T2DM group, A12 allele carriers had larger waist circumference than Pro12Pro genotype carriers;Glucose stimulated insulin secretion by oral glu-cose tolerance test (OGTT) was significantly lower in carriers of the Ala12Ala or Pro12Ala genotype com-pared with Pro12Pro genotype.( Z =2.222, P =0.026; Z =2.051, P =0.040; Z =2.079, P =0.038 ) .⑵There wasn't significant difference among 3 genotypes with 3′-UTR I/D variation in UCP2 gene (χ2 =2.311 , P =0.315 ) .In control group , Glucose stimulated insulin secretion by oral glucose tolerance test ( OGTT) was significantly higher in carriers of the I/D or I/I genotype compared with D/D genotype ( Z =1.997 , P =0.046 ) .⑶The genotype carriers with Pro/Ala +Del/Del were the greatest relation to T2DM (OR=1.22, 95%CI 1.078~1.386).Conclusion Though the UCP2 gene mutation alone or the PPARγ2 gene mutation alone is not associated with T 2DM, the possible additive effects of the two micro genes increase the occurring of T 2DM.
