Insulin protects isolated hearts from ischemia/reperfusion injury: cross-talk between PI3-K/Akt and JNKs / 生理学报

Our previous results have demonstrated that insulin reduces myocardial ischemia/reperfusion (MI/R) injury and increases the postischemic myocardial functions via activating the cellular survival signaling, i.e., phosphatidylinositol 3-kinase (PI3-K)-Akt-endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) cascade. However, it remains largely controversial whether c-Jun NH2-terminal kinase (JNK) is involved in the effects of insulin on MI/R injury. Therefore, the aims of the present study were to investigate the role of JNK, especially the cross-talk between JNK and previously expatiated Akt signaling, in the protective effect of insulin on I/R myocardium. Isolated hearts from adult Sprague-Dawley rats were subjected to 30 min of regional ischemia and followed by 2 or 4 h of reperfusion (n=6). The hearts were pretreated with PI3-K inhibitor LY294002, or phosphorylated-JNK inhibitor SP600125, respectively, then perfused retrogradely with insulin, and the mechanical functions of hearts, including the heart rate (HR), left ventricular developed pressure (LVDP) and instantaneous first derivation of left ventricular pressure (+/-LVdp/dt(max)) were measured. At the end of reperfusion, the infarct size (IS) and apoptotic index (AI) were examined. MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with the control group, insulin treatment in MI/R rats exerted protective effects as evidenced by reduced myocardial IS [(28.9 +/- 2.0)% vs (45.0 +/- 4.0) %, n=6, P<0.01], inhibited cardiomyocyte apoptosis [decreased AI: (16.0 +/- 0.7) % vs (27.6 +/- 1.3) %, n=6, P<0.01] and improved recovery of cardiac systolic/diastolic function (including LVDP and +/-LVdp/dt(max)) at the end of reperfusion. Moreover, insulin resulted in 1.7-fold and 1.5-fold increases in Akt and JNK phosphorylation in I/R myocardium, respectively (n=6, P<0.05). Inhibition of Akt activation with LY294002 abolished, and inhibition of JNK activation with SP600125 enhanced the cardioprotection by insulin, respectively. And the abolishment by LY294002 could be partly converted by SP600125 pretreatment. In addition, SP600125 also decreased the Akt phosphorylation (n=6, P<0.05). These results demonstrate that insulin simultaneously activates both Akt and JNK, and the latter further increases the phosphorylation of Akt which attenuates MI/R injury and improves heart function; this cross-talk between Akt and JNK in the insulin signaling is involved in insulin-induced cardioprotective effect.

Effects of exhaustive exercise on biochemical indexes of endurance-trained mice / 中国应用生理学杂志

<p><b>AIM</b>To observe possible mechanism that endurance training can enhance anti-fatigue capability, and that blood redistribution by analyzing some biochemical indexes of endurance-trained mice after exhaustive exercise.</p><p><b>METHODS</b>The model was set up by exhaustive exercise. The indexes include the activity of SOD, CAT and POD and the MDA content in serum and the NO content in liver, muscle, heart and serum.</p><p><b>RESULTS</b>After exhaustive exercise, the SOD activity in serum and the NO content in liver significantly decrease (P < 0.05 - 0.01), and the activity of POD and CAT, the NO content in serum and muscle significantly increase (P < 0.05 - 0.01), but the rest insignificantly change in non-endurance (P > 0.05). In endurance group, the CAT activity in serum are significantly higher than in non-endurance (P < 0.05), and the NO content in serum is significantly lower than in non-endurance (P < 0.01), but the rest are insignificantly different between two groups (P > 0.05). After 24h restoration, in non-endurance group, the CAT activity and the MDA content in serum and the NO content in liver significantly rise (P < 0.05-0.01), and the NO content in muscle and serum significantly decrease (P < 0.05), but the rest insignificantly change (P > 0.05). In endurance group, the SOD activity in serum and the NO content in liver, serum and heart significantly rise (P < 0.05), and the CAT activity in serum significantly decreases (P < 0.05), but the rest insignificantly change (P > 0.05). In endurance group, the CAT activity and the MDA content in serum are significantly lower than in non-endurance (P < 0.05), but the NO content in heart is higher than in non-endurance (P < 0.05). The rest are insignificantly different between two groups (P > 0.05).</p><p><b>CONCLUSION</b>The possible mechanism, which endurance training can enhance anti-fatigue capability, is relative to enhance the capability to resume balance. Blood redistribution are possibly relative to change to the NO content.</p>

Changes of Activities of Na~+K~+-ATPase,Ca~(2+)Mg~(2+)-ATPase in Erythrocyte Membrane and Blood Viscosity in Children with Essential Hpertension / 实用儿科临床杂志

Objective To study the changes of Na+K+-ATPase,Ca2+Mg2+-ATPase activities in erythrocyte membrane and blood viscosity in children with essential hypertension.Methods The activities of Na+K+-ATPase,Ca2+Mg2+-ATPase in erythrocyte membrane were determined by a colorimetric method.Blood viscosity was measured and analyzed with the statistic analysis SPSS 12.0 software in 50 children from Nov.2004 to Dec.2004 in the people's hospital of guizhou province and adolescents with essential hypertension.Thirty healthy children were collected as control group.Results The activities of Na+ K+-ATPase[(6.12?1.30)?molpi/(gHb?h)and(4.59?1.40)?molpi/(gHb?h)],Ca2+Mg2+-ATPase[(7.46?1.30)?molpi/(gHb?h)and(5.81?1.20)?molpi/(gHb?h)] were lower significantly in hypertension group than those in control group(Pa