| Background and objective:Acute ischemic stroke(AIS)is a major health problem worldwide,which is associated with high mortality and disability.A large number of previous studies have found that the occurrence of AIS has a circadian rhythm,and its peak time is in the morning.Circadian rhythm is regulated by circadian clock genes and their expression products,among which Bmal1(brain and muscle Arnt-like protein)is the core gene of the circadian clock system.Previous studies have demonstrated that Bmal1 plays a regulatory role in the inflammatory response,which plays an important role in the pathological process of cerebrovascular events,especially AIS.Therefore,this study aimed to investigate the circadian pattern of AIS in Taiyuan,Shanxi Province,and to explore its possible mechanism,that is,whether Bmal1 gene can affect the occurrence and development of AIS through inflammatory response.Methods:(1)In this retrospective study,1792 hospitalized patients with acute ischemic stroke diagnosed in secondary and tertiary general hospitals with independent stroke centers in Taiyuan City of Shanxi Province were collected.The patients were divided into four groups:Period 1(0:00-05:59)(298 cases),Period 2(06:00-11:59)(633 cases),Period 3(12:00-17:59)(468 cases)and Period 4(18:00-23:59)(393cases)according to the onset time of stroke.The general data and National Institute of Health stroke scale(NIHSS)score of the four groups were compared and analyzed.In addition,based on the 2-hour interval,the day was divided into 12 2-hour intervals,and the number of AIS cases in each 2-hour interval was counted to clarify the circadian pattern of AIS in Taiyuan area.(2)A total of 100 AIS patients and 100 people without stroke were enrolled as the study group and the control group,respectively.Peripheral venous blood of patients was collected immediately after admission,and mononuclear cells were isolated and extracted.Western Blot was used to detect the expression levels of circadian clock proteins BMAL1 and REV-ERBα.The concentrations of Interleukin-6(IL-6)and Tumor Necrosis Factor-α(TNF-α)in peripheral blood were measured by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of BMAL1 and REV-ERBα and the concentrations of serum inflammatory factors IL-6 and TNF-α were compared between the two groups.According to the onset time of AIS,the patients were divided into four groups: Period1(0:00-05:59),Period 2(06:00-11:59),Period 3(12:00-17:59)and Period 4(18:00-23:59),with 25 cases in each group.The expression levels of circadian clock proteins BMAL1 and REV-ERBα and serum concentrations of IL-6 and TNF-α were compared among the four groups,and the correlation between BMAL1 and REV-ERBα,and the correlation between BMAL1 and IL-6,TNF-α were analyzed.Results:(1)The incidence of AIS was the highest in Period 2(06:00-11:59)in Taiyuan,Shanxi Province,and the circadian rhythm of AIS showed two peaks,the first peak appeared from8:00 am to 9:59 am,and the second peak appeared from 18 PM to 19:59 PM.In addition,patients with AIS onset from 00:00 to 05:59 had the most severe neurological deficits(P<0.05).(2)The protein expression levels of BMALl and REV-ERBα in the AIS group were lower than those in the control group(P<0.05),and the serum concentrations of TNF-α and IL-6 were higher than those in the control group(P<0.05).The expression level of BMALl in AIS was positively correlated with the expression level of REV-ERBα protein(r=0.510,P<0.0001)),and negatively correlated with serum TNF-α and IL-6 concentrations(both P<0.0001,r=-0.631,r=-0.621,respectively).Conclusion:(1)The high incidence of AIS in Taiyuan area of Shanxi Province is in the morning.In addition,the circadian rhythm of AIS showed a bimodal pattern,with the first peak at 8:00-9:59 am and the second peak at 18:00-19:59 am;(2)The circadian clock protein BMAL1 may play an important role in the onset time and rhythm of AIS.The reduction of its expression level may lead to the occurrence of AIS by enhancing the body’s inflammatory response. |
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