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
Objective To investigate the effect of NLRP3/GSDMD/IL-1β pathway in post epileptic depressive behavior of developmental rats and its possible intervention approaches. Methods Sixty SD male rats aged 21 days were randomly divided into negative Control group, status epilepticus (SE) group, and SE+Dexamethasone (SE+DEX) group (20 each). The temporal lobe epilepsy (TLE) model was established by intraperitoneal injection of Lithium chloride-Pilocarpine (Licl-Pilocarpine) in SE group and SE+DEX group, the SE+DEX group was intraperitoneally injected with DEX [3 mg/(kg·d)] after the convulsion ceased for 7 consecutive days. Rats in SE group and Control group were given the same amount of normal saline at the same time point and by the same way. The post epileptic depressive behavior of rats was evaluated by sucrose partiality test (SPT), open field test (OPT) and forced swimming test (FST, n=8). Western blotting and RT-qPCR were used to detect the expression levels of protein and mRNA of NLRP3 and GSDMD in the hippocampus (n=3), and the expression level of IL-1β in the hippocampus was detected by ELISA (n=3). Results Compared with control group, the sucrose consumption rate decreased (68.50%±8.65% vs. 87.13%±3.31%), the time spent in the central area of the open field was reduced [(1.25±0.55) s vs. (4.73±2.57) s], the total movement distance decreased [(7.34±1.48) cm vs. (11.01±1.94) cm], while the immobility time (IMT) in water increased [(53.74±22.54) s vs. (27.18±11.86) s] in SE group; Compared with SE group, the sucrose consumption rate increased (78.8%±2.80% vs. 68.50%±8.65%), the time spent in the central area of the open field was prolonged [(4.00±2.35) s vs. (1.25±0.55) s], while the IMT was reduced [(22.85±7.85) s vs. (53.74±22.54) s] in SE+DEX group. All the differences were statistically significant (P<0.05). The expression levels of protein and mRNA of NLRP3 and GSDMD, as well as the IL-1β content, were significantly higher in SE group than in Control group (P<0.05); While the expression level of mRNA of NLRP3 was lower in SE+DEX group than in SE group (1.40±0.66 vs. 2.70±0.22, P<0.05), but no obviously difference between the two groups on the expression level of NLRP3 protein, The expression levels of GSDMD protein and mRNA were lower in SE+DEX group than in SE group (0.38±0.11 vs. 0.72±0.03, 1.14±0.44 vs. 1.80±0.08), the IL-1β content was also lower than that in SE group [(299.44±119.35) pg/ml vs. (571.37±18.48) pg/ml] with statistically significant difference (P<0.05). Conclusions NLRP3/GSDMD/IL-1β may be involved in the occurrence and development of epilepsy with depression. Short course intervention with dexamethasone may improve epileptic related depressive behavior in developmental rats by down-regulating GSDMD/IL-1β expression.
DOI: 10.11855/j.issn.0577-7402.2020.09.05
Summary Objective The pathophysiology of sudden unexpected death in epilepsy ( SUDEP ) remains undetermined. Seizures are accompanied by respiratory dysfunction ( RD ). Postictal generalized electroencephalography ( EEG ) suppression ( PGES ) may follow generalized tonic–clonic seizures ( GTCS ). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI , we analyzed patients with GTCS in the epilepsy monitoring unit. Method We investigated for associations between PI duration and PGES , ictal/postictal oxygen saturation (SpO 2 ), end‐tidal CO 2 ( ETCO 2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. Results Seventy patients with 181 GTCS and available SpO 2 and/or ETCO 2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO 2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO 2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD . Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO 2 nadir was lower in seizures with PGES (p = 0.046), ETCO 2 peak change (p = 0.003) was higher, and duration of ETCO 2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. Significance The duration of PI and presence of PGES are associated with periictal RD . The duration of PI is also associated with the presence of PGES . Seizure duration or duration of the convulsive phase is not associated with PI or PGES . Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.
Melatonin (MT) has been widely recognized for its ability to mitigate the effects of abiotic stress and regulate plant development. In this study, we investigated the role of exogenous MT in enhancing heat tolerance in sweet potato, with a particular focus on its capacity to alleviate heat stress-induced damage. MT treatment significantly reduced oxidative stress, as evidenced by decreased levels of hydrogen peroxide, superoxide ions, and malondialdehyde (MDA), all of which were elevated under heat stress. To uncover the underlying mechanisms, RNA sequencing was performed on three experimental groups: control (CK), heat stress alone (HS), and MT pre-treatment followed by heat stress (MH). A total of 3491, 3280, and 1171 differentially expressed genes (DEGs) were identified in the CK vs. HS, CK vs. MH, and HS vs. MH comparisons, respectively. MT treatment notably modulated the expression of genes involved in redox regulation and nicotinate and nicotinamide metabolism. Moreover, MT enhanced the expression of genes associated with key signaling pathways, including mitogen-activated protein kinases (MPK3) and plant hormone signal transduction components, such as ethylene response factor (ERF). These findings offer novel insights into the mechanisms by which exogenous MT enhances heat tolerance in sweet potato, highlighting its role in regulating antioxidant systems, metabolic pathways, and hormone signaling. This study presents valuable strategies for improving crop resilience to heat stress.
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