The Effect Of Human Urinary Kallidinogenase On Plasma HMGB1,MMP-9 And TIMP-1 With Acute Cerebral Infarction

Objective: Acute cerebral infarction(ACI)is one of the most common acute diseases in nervous system,and the neurological deficits caused by it are seriously affecting the daily life of patients.Cerebral ischemia can cause a series of neural biochemical changes,including oxidative metabolism disruption,neuronal mitochondrial dysfunction and insufficient energy production.All of these can result in microvascular damage.Then neuroinflammatory cascade is activated which can futher aggravate the brain injury.What’s more,the permeability of the blood-brain barrier(BBB)plays a key role in the ischemic brain injury.In order to explore the effect of human urinary kallidinogenase(HUK)on BBB and the possible mechanism,we observed the changes of plasma high mobility group box 1(HMGB1),matrix metalloproteinase 9(MMP-9)and tissue inhibitor of matrix metalloproteinase1(TIMP-1)in different periods of ACI.Methods:1 One hundred ACI patients in The Second Hospital of Hebei Medical University were enrolled in this study from January 2015 to October 2015,which were randomly divided into HUK group and conventional group.2 The NHISS score were assessed at first day,14 th day and 3rd month.We collected 5ml fasting venous blood,and the concentration of HMGB1,MMP-9,TIMP-1 in plasma were tested by ELISA.Results:1 Distribution:100 patients with ACI were included in the study,all the enrolled patients met the criteria.The patients were randomly divided into the kallikrein group(n=50)and conventional group(n=50).However,22 patients were removed from the experimental process because of the aggravation of the disease and the patients with less cooperation.Finally,45 received HUK,while the other 33 were selected as control.2 The comparison of baseline data: There was no significant difference between the two groups in age,gender,education level,NHISS score before treatment and so on(P>0.05).Thus the patients in the two groups were comparable at admission.3 Evaluation of clinical efficacy: the NIHSS score had no difference at admission,however the score had a decline at 14 th day and 3rd month.And there was a significant difference in the two group(P<0.05).4 The concentration of MMP-9: There was no difference in plasma MMP-9 level between the two groups at admission,but there was a significant difference at 14 th.Compared with the 1th day,the level of plasma MMP-9 in kallikrein group had a significant decline at 14th(P<0.05).However,there was no difference in conventional group(P>0.05).5 The concentration of TIMP-1: There was no difference in plasma TIMP-1 level between the two groups at admission and also at 14th(P>0.05).With the progress of the disease,the level of plasma TIMP-1 were increased gradually both in kallikrein group and conventional group.Besides,there was a significant difference before and after treatment both in the two groups(P<0.05).Furthemore,the level of plasma TIMP-1 of the total patients had a significant difference before and after treatment(P<0.05).6 The concentration of HMGB1: There was no difference in plasma HMGB1 level between the two groups at admission,but there was a significant difference at 14th(P<0.05).With the progress of the disease,the level of plasma HMGB1 in the kallikrein group had a significant decline at14th(P<0.05).Whereas,there was no in conventional group(P>0.05).7 Correlation between plasma TIMP-1 and MMP-9:There was a positive correlation between plasma TIMP-1 and MMP-9 of the total patients at admission(P<0.05,r=0.277),whereas there was uncorrelated at 14th(P>0.05).8 Correlation between plasma HMGB1 and MMP-9: There was uncorrelated between plasma HMGB1 and MMP-9 of the total patients at admission(P>0.05),but had a positive correlation at 14th(P<0.05,r=0.276).Conclusions:1 HUK can significantly improve the short-term and long-term neurological function in patients with ACI.2 HUK can reduce the level of plasma MMP-9 and HMGB1,but it had little effect on TIMP-1.3 HUK is able to protect the brain from damage by lowering the levels of plasma MMP-9 and HMGB1 which can reduce the BBB damage.