Effects of Ischemic Postconditioning on p38MAPK and PLA Expression in Rats With Myocardial Ischemia Reperfusion Injury / 中国循环杂志

Objectives:To explore the possible mechanisms of ischemic postconditioning on alleviating myocardial ischemia-reperfusion injury, focusing on the inflammatory-thrombus related mechanisms. Methods:Rats were randomly divided into six groups (n=10 each):sham group, ischemia-reperfusion injury group, postconditioning group, SB203580 group, anisomycin+postconditioning (Ani+postconditioning) group and anisomycin (Ani) group. After establising the model of myocardial ischemia reperfusion in rats, the levels of myocardial injury markers troponin I (TnI) and creatine kinase isoenzyme (CK-MB), level of leukocyte-platelet aggregation (PLA) were detected by flow cytometry at different time points, myocardial infarction area was measured by using TTC staining and the level of phosphorylation of p38 MAPK (P-p38 MAPK) was determined by Western blot. Results:Compared with the I/R group, the levels of CK-MB, TnI, the infarct size and the expression of PLA at 60 min and 3 h reperfusion were significantly reduced in the postconditioning group and SB203580 group (P＜0.05). Compared with the postconditioning group, the levels of above parameters were significantly higher in the SB203580 group, Ani+postconditioning group and Ani group (P＜0.05). Compared with the I/R group, the expression of P-p38 MAPK in the postconditioning group, SB203580 group, Ani+postconditioning group was significantly reduced (P＜0.05), while it was significantly upregulated in the Ani group (P＜0.05). Furthermore, compared with the postconditioning group, the expression of P-p38 MAPK in the Ani+postconditioning group and Ani group was significantly upregulated (P＜0.05). SB203580 group presented the similar protection effect as the postconditioning group. Cardioprotective effects of postconditioning was partially reduced in the Ani+postconditioning group. Conclusions:Ischemia postconditioning can reduce the expression of PLA during reperfusion by inhibiting the phosphorylation of p38MAPK, thereby attenuating myocardial ischemia-reperfusion injury.

Study on protective effects of platelet-leukocyte aggregation on myocardial ischemia reperfusion injury and postischemic recovery in rats / 天津医药

Objective To observe the effect of postconditioning (PostC) on the expression of platelet-leukocyte aggregation (PLA) during the process of myocardial ischemia and reperfusion in rats, and to explore the mechanisms of ischemic postconditioning (PostC) alleviating myocardial ischemia-reperfusion injury (MIRI). Methods Sixty rats were randomly divided into six groups:sham,reperfusion injury(I/R),postconditioning(PostC),SP600125(inhibition of c-Jun N-terminal kinase,I-JNK),anisomycin and postconditioning(Ani+PostC)and anisomycin(Ani)groups.After constructing the model of myocardial ischemia reperfusion in rats,the levels of myocardial injury markers were detected by using the CK-MB kits and TnI kits. The levels of PLA at different time points were detected by using flow cytometry.The myocardial infarction area were measured by using 2.3.5-Triphenyte-trazoliumchloride(TTC)staining,and the level of phosphorylation of JNK(P-JNK) was determined by using Western blot method. Results (1) The levels of CK-MB, TnI and the infarct size were significantly higher in the I/R group than those in the Sham group(P<0.05).The levels of CK-MB,TnI and the infarct size were significantly lower in the PostC group and I-JNK group than those in the I/R group(P<0.05).Compared with the PostC group,the levels of CK-MB,TnI and the infarct size were significantly higher in the Ani+PostC group and Ani group(P<0.05).(2)Compared with the Sham group,the expression levels of PLA significantly increased in the I/R group at different time points after ischemia (P<0.05). At different time points of MIRI, the expressions of PLA increased gradually in I/R group, Ani+PostC group and Ani group (P<0.05). At the time point of reperfusion for 60 minutes and reperfusion for 3 hours,the expressions of PLA were significantly lower in the PostC group and I-JNK group compared with those of I/R group (P<0.05).Compared with the PostC group,the expressions of PLA were significantly higher in the Ani+PostC group and Ani group (P<0.05). (3) Compared with the Sham group, the expression levels of P-JNK were significantly higher in the I/R group(P<0.05).PostC and I-JNK inhibited the production of P-JNK(P<0.05),while Ani promoted the increase of P-JNK (P<0.05).Compared with the PostC group,the expression levels of P-JNK were significantly higher in the Ani+PostC group and Ani group (P<0.05). Conclusion PostC can reduce the expression of PLA during reperfusion by inhibiting the phosphorylation of JNK,thereby reducing myocardial ischemia-reperfusion injury.

Inhibitory effect of rhynchophylline on human ether-a-go-go related gene channel / 生理学报

We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.

Mutation analysis of a Chinese family with inherited long QT syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation of a Chinese family with inherited long QT syndrome(LQTS).</p><p><b>METHODS</b>The disease-causing gene was tentatively determined in light of the clinical manifestations and electrophysiological properties, and then polymerase chain reaction and DNA sequencing were used for screening and identifying mutation.</p><p><b>RESULTS</b>A missense mutation G940A(G314S) in the KCNQ1 gene was identified, which was the 'hot spot' of long QT syndrome mutation.</p><p><b>CONCLUSION</b>The mutation that is involved with long QT syndrome in Chinese patients is the same as that in the European, American and Japanese patients.</p>

Relationship between congenital long QT syndrome and Brugada syndrome gene mutation / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the molecular pathology in families with long QT syndrome (LQTS) including Jervell-Longe-Nielsen syndrome (JLNS) and Romano-ward syndrome (RWS) and Brugada syndrome (BS) in Chinese population.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, and SCN5A mutation.</p><p><b>RESULTS</b>We identified a novel mutation N1774S in the SCN5A gene of the BS family, a novel mutation G314S in a RWS family which had also been found in Europe, North America, and Japan, and a single nucleotide polymorphisms (SNPs) G643S in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients.</p><p><b>CONCLUSION</b>New mutations were found in our experiment, which expand the spectrum of KCNQ1 and SCN5A mutations that cause LQTS and BS.</p>