GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats

Bin, Zhou; Yanli, Yu; Zhen, Qiu; Qingtao, Meng; Zhongyuan, Xia

doi:10.1590/s0102-865020190110000006

Zhou Bin

PhD, Department of Anesthesiology, Renmin Hospital of Wuhan University, China. Conception and design of the study, acquisition and interpretation of data, statistics analysis, manuscript writing

https://orcid.org/0000-0003-4232-9827

Yu Yanli

PhD, Department of Anesthesiology, Renmin Hospital of Wuhan University, China. Acquisition of data, critical revision

https://orcid.org/0000-0003-4593-773X

Qiu Zhen

Master, Department of Anesthesiology, Renmin Hospital of Wuhan University, China. Analysis and interpretation of data, technical procedures, statistics analysis

https://orcid.org/0000-0002-9859-0963

Meng Qingtao

PhD, Department of Anesthesiology, Renmin Hospital of Wuhan University, China. Acquisition of data, critical revision

https://orcid.org/0000-0002-1936-3050

Xia Zhongyuan Correspondence: Xia Zhongyuan, Department of Anesthesiology, Renmin Hospital of Wuhan University, Jiefang Road 238 Wuhan, Hubei China, Phone: (86) 027-88041911 (82024) xiazhongyuan2005@aliyun.com

Full Professor, Department of Anesthesiology, Renmin Hospital of Wuhan University, China. Design and supervised all phases of the study, final approval

https://orcid.org/0000-0002-5807-9554

Correspondence: Xia Zhongyuan, Department of Anesthesiology, Renmin Hospital of Wuhan University, Jiefang Road 238 Wuhan, Hubei China, Phone: (86) 027-88041911 (82024) xiazhongyuan2005@aliyun.com

Conflict of interest: none

Figures (4)
Tables (3)

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Figure 1
Effects of GDF11 on myocardial infarct size, CK-MB and LDH releases following 30 min ischemia followed by 2 h reperfusion, in non-diabetic and diabetic rats. (A) Percentage of area at risk vs. left ventricle. Biomarkers of the degree of injury (B) CK-MB and (C) LDH release. n=6-8/group. *P≤ 0.05 vs. N+S group, ^#P≤ 0.05 vs. N+IR group, ^&P≤ 0.05 vs. D+S group, ⁺P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; IA/AAR, infarct area/area at risk; CK-MB, creatine kinase MB; LDH, lactate dehydrogenase.

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Figure 2
GDF11 provided cardioprotection by antioxidant stress and up-regulation cardiac autophagy level in diabetic rats. Biomarkers of the degree of oxidative stress (A, B) SOD activity and 15-F2t-isoprostane level were assayed, (C, D) autophagic vacuoles number,(E) LC3II/I ratio and (F) Beclin-1 level in diabetic myocardium was detected to reflect autophagy level. n=6-8/group. *P≤ 0.05 vs. N+S group, ^#P≤ 0.05 vs. N+IR group, ^&P≤ 0.05 vs. D+S group, ⁺P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; SOD, superoxide dismutase.

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Figure 3
Effects of GAF11 on H9c2 cells that suffered HR injury in HG or LG conditions. (A) Results of CCK-8 assay and (B) LDH activity were analyzed. The results are representative of ≥3 independent experiments. *P≤ 0.05 vs. LG group, ^#P≤ 0.05 vs. LG+HR group, ^&P≤ 0.05 vs. HG group, ⁺P≤ 0.05 vs. HG+HR group, ^$P≤ 0.05 vs. GDF11+HG+HR group. LG, low glucose medium; HG, high glucose medium; HR, hypoxia reoxygenation; 3-MA, 3-Methyladenine; CCK-8, cell counting kit-8; LDH, lactate dehydrogenase.

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Figure 4
GDF11 provided protection against HR injury in H9c2 cells exposed to HG by antioxidant stress and elevating autophagy. (A) SOD activity, (B) LDH activity, (C) the ratio of LC3II/I and (D) Beclin-1 expression were analyzed. The results are representative of ≥3 independent experiments. *P≤ 0.05 vs. LG group, ^#P≤ 0.05 vs. LG+HR group, ^&P≤ 0.05 vs. HG group, ⁺P≤ 0.05 vs. HG+HR group, ^$P≤ 0.05 vs. GDF11+HG+HR group. LG, low glucose medium; HG, high glucose medium; HR, hypoxia reoxygenation; 3-MA, 3-Methyladenine; SOD, superoxide dismutase; MDA, malondialdehyde.

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Table 1
Body weights and blood glucose levels of non-diabetic and diabetic rats 8 weeks after STZ induction.

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Table 2
Effects of GDF11 on arrhythmias and mortality in diabetes induced by myocardial IR injury.

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Table 3
Hemodynamic parameters of left ventricular function.

Basic parameters	Non-diabetic	Diabetic
Weight (g)	403.4 ± 18.62	^* * P≤ 0.01 vs. non-diabetic rats.' 215.3 ± 9.08
Blood glucose (mmol/l)	5.27 ± 0.98	^* * P≤ 0.01 vs. non-diabetic rats.' 22.36 ± 4.39

	Ventricular tachycardia		Ventricular fibrillation		Mortality (%)
	Incidence (%)	Duration (s)	Incidence (%)	Duration (s)	Mortality (%)
N+IR	60	23.3 ± 6.0	40	56.9 ±16.0	11
D+IR	^* * P≤ 0.05 vs. N+IR group, 86	^* * P≤ 0.05 vs. N+IR group, 50.1 ± 15.0	^* * P≤ 0.05 vs. N+IR group, 55	^* * P≤ 0.05 vs. N+IR group, 91.1± 16.0	^* * P≤ 0.05 vs. N+IR group, 31
GDF11+D+IR	79	^# # P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; IR, ischemia reperfusion.' 28.2 ± 8.0	51	^# # P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; IR, ischemia reperfusion.' 62.8 ± 17.1	28

	HR (bpm)	LVSP (mmHg)	+dP/dt (mmHg/s)	-dP/dt (mmHg/s)
N+S	395 ± 29	124 ± 20	6402 ± 302	4307 ± 303
N+IR	^* * P≤ 0.05 vs. N+S group, 282 ± 30	^* * P≤ 0.05 vs. N+S group, 70 ± 8	^* * P≤ 0.05 vs. N+S group, 3331 ± 216	^* * P≤ 0.05 vs. N+S group, 2545 ± 407
D+S	^* * P≤ 0.05 vs. N+S group, 332 ± 31	^* * P≤ 0.05 vs. N+S group, 97 ± 15	^* * P≤ 0.05 vs. N+S group, 5338 ± 336	^* * P≤ 0.05 vs. N+S group, 3158 ± 217
D+IR	^# # P≤ 0.05 vs. N+IR group, ^& & P≤ 0.05 vs. D+S group, 214 ± 40	^# # P≤ 0.05 vs. N+IR group, ^& & P≤ 0.05 vs. D+S group, 45 ± 13	^# # P≤ 0.05 vs. N+IR group, ^& & P≤ 0.05 vs. D+S group, 2389 ± 388	^# # P≤ 0.05 vs. N+IR group, ^* * P≤ 0.05 vs. N+S group, 1667 ± 263
GDF11+D+IR	⁺ + P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; HR, heart rate; LVSP, left ventricular systolic pressure; dP/dt, change in LVSP. 306 ± 24	⁺ + P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; HR, heart rate; LVSP, left ventricular systolic pressure; dP/dt, change in LVSP. 64 ± 15	⁺ + P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; HR, heart rate; LVSP, left ventricular systolic pressure; dP/dt, change in LVSP. 3172± 307	⁺ + P≤ 0.05 vs. D+IR group. N, non-diabetes; D, diabetes; S, sham; IR, ischemia reperfusion; HR, heart rate; LVSP, left ventricular systolic pressure; dP/dt, change in LVSP. 2239 ± 282

[1] Correspondence: Xia Zhongyuan, Department of Anesthesiology, Renmin Hospital of Wuhan University, Jiefang Road 238 Wuhan, Hubei China, Phone: (86) 027-88041911 (82024) xiazhongyuan2005@aliyun.com

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GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats¹ 1 Research performed at Central Laboratory, Renmin Hospital of Wuhan University, China.

Abstract

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Conclusion:

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GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats1 1 Research performed at Central Laboratory, Renmin Hospital of Wuhan University, China.

Abstract

Purpose:

Methods:

Results:

Conclusion:

GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats¹ 1 Research performed at Central Laboratory, Renmin Hospital of Wuhan University, China.