Correlative study of autophagy flux and hydrogen sulfide postconditioning protecting on type 2 diabetic rats with myocardial ischemia reperfusion injury

doi:10.3877/cma.j.issn.1674-6880.2016.02.002

Abstract

Abstract:

Objective

To investigate the correlative of autophagy flux and hydrogen sulfide postconditioning protecting against myocardial ischemia reperfusion (I/R) injury in type 2 diabetic rats in vivo.

Methods

Sixty adult male Sprague-Dawley rats were randomly divided into five groups (n=12): sham group, I/R group, chloroquine (CQ) group, sodium hydrosulfide (NaHS) group and CQ + NaHS group. Rats in the sham group only gave thoracotomy and separation of the left anterior descending coronary artery; In the I/R group rats were occluded the left anterior descending coronary artery for 30 min, followed by 4 h of reperfusion; In the CQ group rats received CQ 10 mg/kg by intraperitoneal injection at 1 h before the I/R operation; In the NaHS group rats were injected NaHS 0.05 mg/kg intravenously within 1 min after releasing the left anterior descending coronary artery undergoing 30 min occlusion, then followed by 4 h of reperfusion; and in the CQ + NaHS group rats received CQ 10 mg/kg by intraperitoneal injection at 1 h before the I/R operation additionally on the basis of NaHS group. The heart rate, mean arterial pressure and rate-pressure product (RPP) were detected and recorded at 15 min of balance period, ischemic period, and 1, 2, 4 h after reperfusion. After reperfusion for 4 h, the rats were sacrificed and the hearts were used to calculate the range of myocardial infarction and the express of microtubule-associated protein 1 light chain 3 (LC3), Cathepsin B, Beclin-1 and P62 were determined by Western blotting.

Results

The heart rates in the five groups had no siginficant differences at each time point (F=0.854, P=0.512), but the mean arterial pressure and RPP showed siginficant differences among the five groups at each time point (F=5.182, P=0.007; F=5.082, P=0.008). Furthermore, the mean arterial pressure[(87 ± 8) mmHg vs. (72 ± 10) mmHg, (91±10) mmHg vs. (63 ± 6) mmHg] and RPP [(35.4 ± 4.6)·10³ mmHg·beat/min vs. (28.7 ± 5.8)·10³ mmHg·beat/min, (36.2 ± 5.8)·10³ mmHg·beat/min vs. (26.8 ± 3.8)·10³ mmHg·beat/min] in the NaHS group at 2, 4 h after reperfusion were much higher than those in the I/R group (all P<0.05). The range of myocardial infarction and the express of LC3, Cathepsin B, Beclin-1 and P62 at 4 h after reperfusion all had statistical significance obviously among five groups (F=96.907, 71.164, 43.594, 57.180, 35.967, all P<0.05) , and above indicators in the NaHS group were much lower than those in the I/R group, CQ group and CQ + NaHS group (all P<0.05).

Conclusion

Hydrogen sulfide postconditioning play a protective role through repairinng autophagy flux in type 2 diabetic rats with I/R injury.

Key words: Hydrogen sulfide, Ischemic postconditioning, Myocardial reperfusion injury, Diabetes mellitus, type 2, Autophagy, Rats

Wenjie Zhao, Chen Wang, Bo Sun, Haihua Shan, An Wang, Shigang Qiao. Correlative study of autophagy flux and hydrogen sulfide postconditioning protecting on type 2 diabetic rats with myocardial ischemia reperfusion injury[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2016, 09(02): 81-86.

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Figures/Tables 6

References 20

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组别		例数	平衡期	缺血期	再灌注期1 h	再灌注期2 h	再灌注期4 h
心率（min^-1）		?	?	?	?	?	?
?	假手术组	8	392 ± 32	382 ± 49	393 ± 51	382 ± 37	381 ± 38
?	I/R组	8	388 ± 45	385 ± 39	379 ± 51	381 ± 41	375 ± 37
?	CQ组	8	382 ± 51	375 ± 47	382 ± 44	379 ± 58	388 ± 35
?	NaHS组	8	388 ± 47	385 ± 41	379 ± 53	381 ± 43	375 ± 39
?	NaHS + CQ组	8	380 ± 32	386 ± 57	382 ± 52	385 ± 28	377 ± 46
平均动脉压（mmHg）		?	?	?	?	?	?
?	假手术组	8	118 ± 15	115 ± 16	110 ± 10	113 ± 12	110 ± 17
?	I/R组	8	122 ± 17	102 ± 11^a	88 ± 12^a	72 ± 10^a	63 ± 6^a
?	CQ组	8	123 ± 16	108 ± 13^a	90 ± 9^a	75 ± 14^ab	65 ± 9^ab
?	NaHS组	8	125 ± 18	101 ± 9^a	99 ± 10^a	87 ± 8^ac	91 ± 10^ac
?	NaHS + CQ组	8	124 ± 12	103 ± 12^a	92 ± 11^a	76 ± 10^ab	66 ± 12^ab
RPP（次·mmHg·10³/min）		?	?	?	?	?	?
?	假手术组	8	48.8 ± 5.8	47.8 ± 7.2	45.0 ± 7.1	45.5 ± 8.0	44.6 ± 8.3
?	I/R组	8	51.2 ± 8.2	42.3 ± 6.5^a	38.8 ± 6.3^a	28.7 ± 5.8^a	26.8 ± 3.8^a
?	CQ组	8	51.3 ± 7.8	41.9 ± 6.8^a	38.6 ± 7.1^a	28.8 ± 6.2^ab	27.4 ± 6.3^ab
?	NaHS组	8	48.8 ± 8.5	42.9 ± 7.1^a	39.9 ± 7.5^a	35.4 ± 4.6^ac	36.2 ± 5.8^ac
?	NaHS + CQ组	8	49.5 ± 8.0	42.8 ± 8.6^a	39.4 ± 4.5^a	30.2 ± 4.6^ab	26.5 ± 4.8^ab

组别		例数	平衡期	缺血期	再灌注期1 h	再灌注期2 h	再灌注期4 h
心率（min^-1）		?	?	?	?	?	?
?	假手术组	8	392 ± 32	382 ± 49	393 ± 51	382 ± 37	381 ± 38
?	I/R组	8	388 ± 45	385 ± 39	379 ± 51	381 ± 41	375 ± 37
?	CQ组	8	382 ± 51	375 ± 47	382 ± 44	379 ± 58	388 ± 35
?	NaHS组	8	388 ± 47	385 ± 41	379 ± 53	381 ± 43	375 ± 39
?	NaHS + CQ组	8	380 ± 32	386 ± 57	382 ± 52	385 ± 28	377 ± 46
平均动脉压（mmHg）		?	?	?	?	?	?
?	假手术组	8	118 ± 15	115 ± 16	110 ± 10	113 ± 12	110 ± 17
?	I/R组	8	122 ± 17	102 ± 11^a	88 ± 12^a	72 ± 10^a	63 ± 6^a
?	CQ组	8	123 ± 16	108 ± 13^a	90 ± 9^a	75 ± 14^ab	65 ± 9^ab
?	NaHS组	8	125 ± 18	101 ± 9^a	99 ± 10^a	87 ± 8^ac	91 ± 10^ac
?	NaHS + CQ组	8	124 ± 12	103 ± 12^a	92 ± 11^a	76 ± 10^ab	66 ± 12^ab
RPP（次·mmHg·10³/min）		?	?	?	?	?	?
?	假手术组	8	48.8 ± 5.8	47.8 ± 7.2	45.0 ± 7.1	45.5 ± 8.0	44.6 ± 8.3
?	I/R组	8	51.2 ± 8.2	42.3 ± 6.5^a	38.8 ± 6.3^a	28.7 ± 5.8^a	26.8 ± 3.8^a
?	CQ组	8	51.3 ± 7.8	41.9 ± 6.8^a	38.6 ± 7.1^a	28.8 ± 6.2^ab	27.4 ± 6.3^ab
?	NaHS组	8	48.8 ± 8.5	42.9 ± 7.1^a	39.9 ± 7.5^a	35.4 ± 4.6^ac	36.2 ± 5.8^ac
?	NaHS + CQ组	8	49.5 ± 8.0	42.8 ± 8.6^a	39.4 ± 4.5^a	30.2 ± 4.6^ab	26.5 ± 4.8^ab

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