1.Clinical significance of plasma TNF-α and ET levels in patients with subarachnoid hemorrhage
Sibei JI ; Xiaojun TIAN ; Hehua LI ; Zhixiu SONG ; Kaihua ZHAI ; Mingxin MA
Clinical Medicine of China 2008;24(12):1188-1190
Objective To study the plasma TNF-α and endothelin (ET) levels in patient with subarach-noid hemorrhage(SAH). Methods The plasma TNF-α and ET levels were measured by ELISA and radioimmunity at 1,3,7,14 and 21 d after onset of SAH in 45 patients. Results The plasma TNF-α and ET levels in patients with SAH were higher than the normal controls(P<0.01),among which the highest levels appeared at 3 d and 7 d,and the levels of plasma TNF-α and ET in patients with SAH were decreased at 14 d. Those of high Hunt-Hess grade~groups was higher than those of lower grade~groups(P<0.01). Conclusion The plasma TNF-α and ET levels are significantly elevated in the patients with SAH,which suggests that TNF-α and ET may play an important role in the pathogenesis of SAH,and which suggests that is one of the possible ways to prevent and treat cardiovascular spasm (CVS) after SAH by inhibiting TNF-α and ET.
2.Effect of Shuanglu Tongnao Formula on Neuronal Ferroptosis in Ischemic Stroke Rats by Regulating the SIRT1/Nrf2/GPx4 Signaling Pathway
Guangshan ZHENG ; Yang ZHAI ; Kaihua WANG ; Wei MA ; Xiaoping MEI ; Ying CHEN ; Min ZOU ; Yan PANG ; Peng YANG ; Yan LYU
Herald of Medicine 2024;43(4):526-534
Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.