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.

Preliminary structural and functional study on a novel gene HSPCSET / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To characterize the structural and the functional feature of a novel gene HSPCSET isolated from human CD34+ hematopoietic stem/progenitor cells (HS/PCs).</p><p><b>METHODS</b>Bioinformatic technology was used to identify the structural features of the HSPCSET protein and perform the multiple sequence alignment. Yeast-two-hybrid system was used to identify the proteins interacting with the HSPCSET protein. After sequencing, we selected out the positive clones which had clear functions, and carried out beta-gal experiment and GST pull down assay to confirm the results. The cellular location of the HSPCSET was checked by immunofluorescence assay.</p><p><b>RESULTS</b>The HSPCSET protein belongs to a SET domain family, which is evolutionarily conserved across species. It implied that HSPCSET may have biologically important function. Using yeast-two-hybrid system, we showed that the protein sequence with SET domain might bind to 13 proteins, which involved in signaling transduction, transcriptional regulation, apoptosis, tumorigenesis, development, etc. And 4 proteins (GADD34, SIVA, DNAJ and PHF1) were confirmed by one-on-one back of the hybrid experiment, beta-gal test and GST pull down assay. When GADD34 and HSPCSET were co-transfected, they co-localized in the nucleus, suggesting a strong interaction.</p><p><b>CONCLUSION</b>The novel gene HSPCSET is likely to have biologically important function. This study provides the basis for further studies of its function in hematopoiesis and tumorigenesis.</p>

Association of aldosterone synthase gene -344 T/C polymorphism with early renal damage in Han nationality with essential hypertension / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the -344T/C polymorphism of aldosterone synthase gene is associated with early renal damage in Han nationality with essential hypertension in Shandong province.</p><p><b>METHODS</b>Plasma aldosterone concentration and urinary albumin excretion were measured with radioimmunoassays in 225 patients with essential hypertension, and hypertensives were classified as hypertension with normal albuminuria or hypertension with microalbuminuria according to urinary albumin excretion during 24 hours. -344T/C polymorphism of aldosterone synthase gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in controls and hypertensives.</p><p><b>RESULTS</b>No significant differences were found in genotype distribution among groups of control, primary hypertension with normal albuminuria and hypertension with microalbuminuria. The C allele frequency in hypertension with microal buminuria group was significantly higher than that in control and hypertension with normal albuminuria group (P < 0.05). In hypertensive patients, plasma aldosterone concentration and urinary albumin excretion of TC+CC genotypes were significantly higher than that of TT genotype ( P< 0.05).</p><p><b>CONCLUSION</b>These results suggest that -344T/C polymorphism of aldosterone synthase gene may be associated with early renal damage in Han nationality with essential hypertension, C allele may be a genetic factor susceptible to renal damage in hypertensives.</p>

Associations between CYP11B2 gene -344T/C polymorphism and essential hypertension in the Han nationality in Shandong province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the -344T/C polymorphism of CYP11B2 gene is associated with essential hypertension in the Hans in Shandong province.</p><p><b>METHODS</b>Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured with radioimmunoassays; the hypertensives were classified as low-renin and normal- or high-renin group by PAC/PRA ratio. -344T/C polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) in controls and hypertensives.</p><p><b>RESULTS</b>No significant differences were found in genotype distribution or allele frequency between groups of control and primary hypertension or between groups of control and normal- or high-renin hypertension. The C allele frequency in low-renin hypertension group was significantly higher than that in normotensives and normal- or high-renin hypertension group (P < 0.05).</p><p><b>CONCLUSION</b>These results suggest that -344T/C polymorphism of CYP11B2 gene may be associated with low-renin essential hypertension in the Han nationality in Shandong province.</p>