Abstract:

Objective: To study the hypothesis about the pharmacological post-conditioning with lactic acid and saturated hydrogen saline after ischemic injury of myocardium instead of post-conditioning with mechanical dilatation of severely occluded coronary vessels to attenuate apoptosis of cardiocyte by mitogenactivated protein kinases (MAPK) pathway. Methods: A total of 108 rats were randomly (random number) divided into 6 groups (re = 18 in each group): sham operated group (received 60 pX normal saline without ischemia), reperfusion/injury group (R/I, received 60 pX normal saline solution and routine ischemicreperfusion [IR] procedure), post-conditioning group (M-Post, received 60 pX normal saline and postconditioning treatment, 4 cycles of 20/20 s of reperfusion/re-occlusion), lactic acid group (Lac, received 60 |xL lactic acid and routine IR procedure), saturated hydrogen saline group (Hyd, received 60 pX hydrogen rich saline and routine IR procedure), and lactic acid + saturated hydrogen saline group (Lac + Hyd, received a combination of 60 pX of lactic acid and 60 μL of hydrogen rich saline along with routine IR procedure). Acute myocardial infarction model was made by ischemia for 45 min, and pH value of blood from right atrium was detected in rats of all groups. After 3 min reperfusion, 6 rats of each group were sacrificed and myocardial tissue was taken out to measure the level of MDA and SOD. After 30 min reperfusion, other 6 rats of each group were sacrificed and myocardial tissue was taken out to measure the level of phosphorylated MAPK (p38/JNK and ERK), TNF-a, Caspase-8 by Western-blot method. After 24 h reperfusion, there were only 6 rats in each group, and hemodynamics were measured in each rat, and then rats were sacrificed and hearts were taken out to detect cell apoptosis by TUNEL method. A one-way analysis of variance (ANOVA) was used, and q tests were employed to determine if any significant differences in individual variable existed between groups. Results: The pH of blood from right atrium after 3 min of reperfusion in Lac + Hyd group was significantly lower than that in R/I group (7. 32 ±0. 06 vs. 7. 43 ±0. 03, P <0. 05), the content of MDA was lower (1. 14 ± 0.16 vs. 1. 56 ± 0. 21, P < 0. 05) and the content of SOD was higher in Lac + Hyd group than those in R/I group (57. 92 ± 15. 12 vs. 35. 48 ± 12. 46, P < 0. 05). Apoptotic index of Lac + Hyd group was much lower than that of R/I group (9. 50 ± 1. 51) % vs. (15. 21 ± 1.91)%, P<0.05. After 30 min of reperfusion, the level of P-p38 in ischemic myocardia in Lac + Hyd group was significantly lower than that in R/I group (0. 46 ±0. 06 vs. 2. 18 ±0. 32, P <0. 05), the levels of P-JNK (0.59 ±0.03 vs. 1.62 ±0.29, P<0.05), TNFa (0.34 ±0.08 vs. 1.78 ±0.31, P<0.05) and Caspase-8 (0. 31 ±0. 07 vs. 1. 52 ± 0. 28, P 0. 05). After 30 min of reperfusion, there was no significant difference in the level of P-ERK between Lac + Hyd group and R/I group (0. 55 ± 0. 13 vs. 0. 57 ± 0. 05, P > 0. 05), and the level of P-ERK in Hyd group was significantly lower than that in R/I group (0. 30 ± 0. 09 vs. 0. 57 ± 0. 05, P < 0. 05), And the level of P-ERK in Lac Hyd and Lac + Hyd groups was significantly lower than that in M-Post group (1.21 ± 0.13, 0. 30 ± 0.09, 0. 55 ± 0.13 vs. 1. 96 ± 0. 39, P < 0.05). Conclusion: Pharmacological post-conditioning with lactic acid and saturated hydrogen saline could be used instead of mechanical post-conditioning to inhibit the phosphorylation of p38/JNK and ERK, attenuating myocardial cell apoptosis.

Read more:

https://doi.org/10.3760/cma.j.issn.1671-0282.2015.03.014

Related Articles: