1.A novel hydrogen sulfide donor modulates Kir6.2 via the cyclic guanosine monophosphate- dependent protein kinase signaling pathway in one side hippocampus of epileptic rats
Danqiong LIU ; Ziting ZHU ; Sheng DU ; Peiye CHEN ; Manru GUO ; Yilong ZHANG ; Yanmei SU ; Guanqi WANG ; Pingyi XU ; Xiaoqin ZHU
Chinese Journal of Neurology 2021;54(3):242-250
Objective:To explore the effect of hydrogen sulfide (H 2S) on modulating the subunit Kir6.2 of adenosine triphosphate sensitive potassium channels via the cyclic guanosine monophosphate-dependent protein kinase (cGMP/PKG) signaling pathway in epileptic rat models. Methods:Sixty adult male SD rats were randomly divided into the following six groups (10 rats in each group) by random number table method: control, epileptic, H 2S donor, H 2S donor+epileptic, KT5823 (one inhibitor of the cyclic guanosine monophosphate-dependent protein kinase)+H 2S donor+epileptic, and glibenclamide (one inhibitor of the adenosine triphosphate sensitive potassium channels)+H 2S donor+epileptic groups. Except the control group, SD rats were intraperitoneally injected with plentylenetetrazole to make the kindling models and their behaviours were recorded including the latency period, the grade, and the duration of the first epileptic seizure according to the Racine′s standard. The waveforms of electroencephalogram (EEG) in hippocampus were also recorded during the seizure. The mRNA and protein levels of PKG and Kir6.2 in hippocampus were evaluated by Western blotting and quantitative real-time polymerase chain reaction, and the hippocampal concentrations of cGMP and phosphorylation of cyclic guanosine monophosphate-dependent protein kinase (p-PKG) were detected by enzyme linked immunosorbent assay. Results:Rats in the epileptic group showed Ⅳ-Ⅴ grade of epileptic seizure [4.500 (4.000, 4.875)], short latency period [(10.37±8.21) min] but long duration [(69.50±24.37) s] of seizure. Compared to the epileptic group, rats in the H 2S donor group showed Ⅱ-Ⅲ grade of epileptic seizure ( P=0.004), significantly longer latency period ( P<0.001), and shorter duration of seizure ( P<0.001). Compared to the H 2S donor+epileptic group, rats in the KT5823+H 2S donor+epileptic group showed Ⅲ-Ⅳ grade of epileptic seizures, significantly shorter latency period ( P<0.001), and longer duration of seizure ( P<0.001). The results of EEG showed that the wave patterns in the epileptic group were spike or sharp waves and the amplitudes were largest [(190.570±23.590) μV]. Compared with the epileptic group, amplitudes were reduced ( P<0.001) in the H 2S donor+epileptic group. PKG mRNA and PKG protein were expressed differently among all groups (PKG mRNA: n=5, H=26.714, P<0.001; PKG protein: n=5, F=30.597, P<0.001). Compared with the control group, the expression of both PKG mRNA and PKG protein was decreased (PKG mRNA: 1.000±0.001 vs 0.782±0.064, P=0.023; PKG protein: 0.550±0.037 vs 0.145±0.020, P=0.042) in the epileptic group. Besides, Kir6.2 mRNA and Kir6.2 protein were expressed differently among all groups (Kir6.2 mRNA: n=5, H=27.761, P<0.001; Kir6.2 protein: n=5, F=60.659, P<0.001). Compared with the control group, the expression of both Kir6.2 mRNA and Kir6.2 protein was decreased (Kir6.2 mRNA: 1.000±0.001 vs 0.897±0.033, P=0.004; Kir6.2 protein: 0.384±0.035 vs 0.215±0.016, P=0.024) in the epileptic group. And the concentrations of cGMP and p-PKG were decreased (cGMP: P<0.001; p-PKG: P<0.001) in the epileptic group. The results in the H 2S donor+epileptic group were up-regulated (PKG mRNA: P=0.047; PKG protein: P<0.001; Kir6.2 mRNA: P=0.011; Kir6.2 protein: P<0.001; cGMP: P<0.001; p-PKG: P<0.001) compared with the epileptic group. However, the results in the KT5823+H 2S donor+epileptic group were down-regulated (PKG mRNA: P=0.015; PKG protein: P=0.027; Kir6.2 mRNA: P=0.013; Kir6.2 protein: P=0.017; cGMP: P=0.005; p-PKG: P<0.001) compared with the H 2S donor+epileptic group. Conclusion:A possible mechanism is that H 2S prevents the epileptic seizure from modulating the subunit Kir6.2 of ATP sensitive potassium channels via the cGMP/PKG signaling pathway.
2.Influence of glomerular filtration rate of living donor on recovery of graft function after transplantation
Ziting SU ; Zhen LI ; Zhong ZENG ; Tao LIU ; Jian DUAN ; Hanfei HUANG ; Jie LIN
Organ Transplantation 2015;(5):331-334,339
Objective To investigate the influence of glomerular filtration rate (GFR)of living donor on recovery of graft function after transplantation.Methods Clinical data of 108 pairs of donors and recipients undergoing living donor renal transplantation at the Organ Transplantation Center of First Affiliated Hospital of Kunming Medical University from 2009 to 2013 were retrospectively studied.The objects were divided into G1 group (GFR <40 ml/min),G2 group(GFR 40 ~45 ml/min),G3 group(GFR 46 ~50 ml/min)and G4 group (GFR >50 ml/min)according to GFR of the donor kidneys.Changes in serum creatinine (Scr)at 1 week,2 weeks,3 weeks,1 month,3 months,6 months and 1 year after transplantation as well as survival conditions of patient and kidney within 1 year after transplantation of each group were compared.Results Compared with G1 group,Scr at 2 weeks,3 weeks,1 month after transplantation was lower in G2 group,G3 group and G4 group,and the difference had statistical significance (all in P <0.05).As for survival conditions of patient and kidney within 1 year after transplantation,one patient in G1 group developed graft failure due to hyperacute rejection and one patient in G1 group died of severe pulmonary infection.One patient in G2 group developed graft failure due to acute rejection.One patient in G3 group died of severe pulmonary infection.One patient in G4 group died of severe pulmonary infection. Other patients and grafts survived during the follow-up.Conclusions Low GFR of living kidney donor has certain influence on recovery of graft function in the early stage (within one month)after renal transplantation.