Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and...Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and cardiovascular diseases. In the present study, we aimed to investigate the association between circulating levels of high sensitive C-reactive protein (hs-CRP) and various biomarkers for hepatic, diabetic, and cardiovascular health. The retrospective analysis included 438 individuals who were tested for these panels simultaneously at Vibrant America Clinical Laboratory. The study population included free-living individuals without any preexisting clinical conditions. Among the cardiovascular markers, a positive correlation and significant association was found between high levels of hs-CRP and serum levels of triglycerides (r = 0.0964, p −0.1423, p −0.1216, p < 0.0105) with circulating levels of hs-CRP. Among all the diabetic markers, glucose (r = 0.1547, p < 0.0011) and glycated serum protein (r = 0.1725, p < 0.0003) were positively correlated with circulating hs-CRP. In the hepatic panel, AST, a transaminase that plays a vital role in amino acid metabolism, was found to have a strong positive correlation with hs-CRP (r = 0.2139, p < 0.0001). In conclusion, the results clearly show the association of hs-CRP with diabetic, hepatic, and cardiovascular risk factors indicating its central value as a key marker for several lifestyle-associated disorders.展开更多
This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CR...This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CRP) levels in patients undergoing carotid endarterectomy(CEA). Carotid CEUS was performed preoperatively in 115 patients who would undergo CEA, and the enhancement degree of the carotid plaques was evaluated by both the visual semiquantitative analysis and the quantitative time-intensity curve analysis. Serum hs-CRP levels were detected using the particle-enhanced immunoturbidimetric assay also before the operation. Additionally, the carotid plaque samples were subjected to histopathological examination postoperatively. The density of neovessels and the number of macrophages in the plaques were assessed by immunohistochemistry. The results showed that among the 115 patients, grade 0 plaque contrast enhancement was noted in 35 patients, grade 1 in 48 patients and grade 2 in 32 patients. The degree of plaque enhancement, the density of neovessels, the number of macrophages, and the hs-CRP levels were highest in the grade 2 patients. Correlation analysis showed that the enhancement degree of the carotid plaques was closely related to the immunohistochemical parameters of the plaques and the serum hs-CRP levels. It was suggested that the carotid plaque enhancement on CEUS can be used to evaluate the vulnerability of carotid plaques.展开更多
Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in at...Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.展开更多
BACKGROUND: Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE: To detect the levels o...BACKGROUND: Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE: To detect the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor- a (TNF- α ) in elderly males with cerebral infarction. DESIGN: Non-randomized current control study. SETTING: Cadre Medical Department, Guizhou Provincial People's Hospital. PARTICIPANTS: Forty elderly males (65-89 years old) with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People's Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients (65-87 years old) without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group (P 〉 0.05), and this suggested that the baseline data of both groups were comparable. METHODS: Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF- α in the serum. MAIN OUTCOME MEASURES: The levels of hs-CRP, 1L-6, and TNF- α in the serum in both groups. RESULTS: Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss. Levels of hs-CRP, IL-6, and TNF-α in the cerebral infarction group were significantly higher than those in the control group (P 〈 0.01 ). CONCLUSION: Levels of serum inflammatory reactive factors are increased in elderly males with cerebral infarction.展开更多
Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This stu...Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This study assessed roles of insulin and glucagon in its onset and remission. Methods: Plasma glucose, insulin and glucagon were determined after an overnight fast and repeatedly until 180 minutes on ingestion of 3 meals;100 g glucose;100 g pure protein liquid and mixture of 50 g each at 14 days’ interval. Five adults with IRH and 6 age matched healthy volunteers participated. Results: In IRH, glucose ingestion induced prompt rise in glucose (5.1 ± 0.8 to10.5 ± 1.2 mM/L) followed later by hypoglycemia (2.6 ± 0.4 mM/L). Insulin rose from 7 ± 2 to 90 ± 18 mU/L. Glucagon rose initially (10% ± 2%) from elevated basal concentration (373 ± 57 mU/L) followed by later decline (-43% ± 12%). On protein ingestion, glucose declined followed by a restoration to basal level while both insulin and glucagon rose (28 ± 6 mU/L;148% ± 38%, p < 0.01). However, insulin response was lower and glucagon rise was greater when compared to responses on glucose ingestion (p < 0.01). With mixed meal, glucose (8.2 ± 0.6 mM/L), insulin (65 ± 12 mU/L) and glucagon (48% ± 7%) responses were lesser than rises following glucose ingestion (p < 0.05) and hypoglycemia did not occur. Conclusion: In IRH, initial hyperglycemia on glucose ingestion may be exacerbated by paradoxical glucagon rise and hypoglycemia may be induced by increased insulin and declining glucagon responses. Resolution of hypoglycemia with high protein low carbohydrate diet may be attributed to blunting of insulin response and concurrent glucagon rise.展开更多
Objective To describe the distribution of plasma high sensitivity C-reactive protein (hsCRP) and explore the relationship between hsCRP and metabolic risk factors among residents living in longevity areas of China. ...Objective To describe the distribution of plasma high sensitivity C-reactive protein (hsCRP) and explore the relationship between hsCRP and metabolic risk factors among residents living in longevity areas of China. Methods 268 individuals aged between 40 and 59 years and 506 individuals aged over 90 years were selected from 5 longevity areas of China to participate in a cross section longitudinal cohort study. The participants were interviewed with general health related questionnaire to collect their demographic, behavioral and lifestyle data, as well as their chronic conditions, and meanwhile their physical and biomedical parameters including waist circumference (WC), blood pressure (BP), hsCRP, plasma lipids, and fasting blood glucose (FBG) were measured. Results The median of hsCRP was 0.99 mg/L in the middle-aged group and 2.76 mg/L in the oldest old group. No significant gender difference was observed between the above two groups. Among the oldest old individuals, 36.56% had an hsCRP level 〉3.0 mg/L. The prevalence of high hsCRP was 26.79% in the middle-aged group. The results of stepwise multiple linear regression analyses showed that HDL-C was independently associated with In (hsCRP) concentration in the middle-aged group, whereas In (TG), HDL-C and FBG were correlated after adjustment for gender, study site, smoking, drinking, education and BMI in the oldest old group. Conclusion HDL-C is a stronger predictor of elevated hsCRP than other metabolic factors in the middle-aged population. For the oldest old persons, high TG, low HDL-C, and FBG predict elevated plasma hsCRP.展开更多
Objective:To explore the application value of neutrophil/lymphocyte ratio (NLR) combined with high sensitive C reactive protein (hs-CRP) in the evaluation of community acquired pneumonia (CAP). Methods:From November 2...Objective:To explore the application value of neutrophil/lymphocyte ratio (NLR) combined with high sensitive C reactive protein (hs-CRP) in the evaluation of community acquired pneumonia (CAP). Methods:From November 2015 to October 2016, 58 cases of CAP patients admitted in our department were selected as research objects and were divided into low risk group and high risk group according to the PSI score and CURB-65 standard for evaluation. They were divided into improved group (48 cases) and death group (10 cases) according to prognosis. Hs-CRP was determined by immunoturbidimetric assay, procalcitonin (PCT) by immunofluorescence, NLR by count method of laser scattering, and white blood (WBC) was counted. The differences in WBC, PCT, NLR and hs-CRP between different risk groups were compared, and the correlation was evaluated using Spearman's rank correlation analysis method. The changes in indexes were observed in the improved and death cases. Results:The high risk group had higher NLR, PCT and hs-CRP than low risk group (P<0.05), while no significant difference was found in WBC (P>0.05). No correlation was found between NLR and WBC, while a strong correlation was found between hs-CRP and PCT. The WBC, PCT, NLR and hs-CRP levels were significantly lower in the improved group than the death group (P<0.05). Conclusions:NLR combined with hs-CRP, WBC, and PCT has a good assessment of the severity of CAR, and high levels of NLR, hs-CRP, WBC, and PCT predict the severity of the disease and poor prognosis.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
文摘Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and cardiovascular diseases. In the present study, we aimed to investigate the association between circulating levels of high sensitive C-reactive protein (hs-CRP) and various biomarkers for hepatic, diabetic, and cardiovascular health. The retrospective analysis included 438 individuals who were tested for these panels simultaneously at Vibrant America Clinical Laboratory. The study population included free-living individuals without any preexisting clinical conditions. Among the cardiovascular markers, a positive correlation and significant association was found between high levels of hs-CRP and serum levels of triglycerides (r = 0.0964, p −0.1423, p −0.1216, p < 0.0105) with circulating levels of hs-CRP. Among all the diabetic markers, glucose (r = 0.1547, p < 0.0011) and glycated serum protein (r = 0.1725, p < 0.0003) were positively correlated with circulating hs-CRP. In the hepatic panel, AST, a transaminase that plays a vital role in amino acid metabolism, was found to have a strong positive correlation with hs-CRP (r = 0.2139, p < 0.0001). In conclusion, the results clearly show the association of hs-CRP with diabetic, hepatic, and cardiovascular risk factors indicating its central value as a key marker for several lifestyle-associated disorders.
基金supported by the Natural Science Foundation of Zhejiang Province,China(No.LY13H180007)
文摘This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CRP) levels in patients undergoing carotid endarterectomy(CEA). Carotid CEUS was performed preoperatively in 115 patients who would undergo CEA, and the enhancement degree of the carotid plaques was evaluated by both the visual semiquantitative analysis and the quantitative time-intensity curve analysis. Serum hs-CRP levels were detected using the particle-enhanced immunoturbidimetric assay also before the operation. Additionally, the carotid plaque samples were subjected to histopathological examination postoperatively. The density of neovessels and the number of macrophages in the plaques were assessed by immunohistochemistry. The results showed that among the 115 patients, grade 0 plaque contrast enhancement was noted in 35 patients, grade 1 in 48 patients and grade 2 in 32 patients. The degree of plaque enhancement, the density of neovessels, the number of macrophages, and the hs-CRP levels were highest in the grade 2 patients. Correlation analysis showed that the enhancement degree of the carotid plaques was closely related to the immunohistochemical parameters of the plaques and the serum hs-CRP levels. It was suggested that the carotid plaque enhancement on CEUS can be used to evaluate the vulnerability of carotid plaques.
文摘Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.
基金Educational and Technological Foundation for Excellent Talents of Guizhou Province, No. 2005(25)
文摘BACKGROUND: Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE: To detect the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor- a (TNF- α ) in elderly males with cerebral infarction. DESIGN: Non-randomized current control study. SETTING: Cadre Medical Department, Guizhou Provincial People's Hospital. PARTICIPANTS: Forty elderly males (65-89 years old) with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People's Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients (65-87 years old) without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group (P 〉 0.05), and this suggested that the baseline data of both groups were comparable. METHODS: Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF- α in the serum. MAIN OUTCOME MEASURES: The levels of hs-CRP, 1L-6, and TNF- α in the serum in both groups. RESULTS: Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss. Levels of hs-CRP, IL-6, and TNF-α in the cerebral infarction group were significantly higher than those in the control group (P 〈 0.01 ). CONCLUSION: Levels of serum inflammatory reactive factors are increased in elderly males with cerebral infarction.
文摘Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This study assessed roles of insulin and glucagon in its onset and remission. Methods: Plasma glucose, insulin and glucagon were determined after an overnight fast and repeatedly until 180 minutes on ingestion of 3 meals;100 g glucose;100 g pure protein liquid and mixture of 50 g each at 14 days’ interval. Five adults with IRH and 6 age matched healthy volunteers participated. Results: In IRH, glucose ingestion induced prompt rise in glucose (5.1 ± 0.8 to10.5 ± 1.2 mM/L) followed later by hypoglycemia (2.6 ± 0.4 mM/L). Insulin rose from 7 ± 2 to 90 ± 18 mU/L. Glucagon rose initially (10% ± 2%) from elevated basal concentration (373 ± 57 mU/L) followed by later decline (-43% ± 12%). On protein ingestion, glucose declined followed by a restoration to basal level while both insulin and glucagon rose (28 ± 6 mU/L;148% ± 38%, p < 0.01). However, insulin response was lower and glucagon rise was greater when compared to responses on glucose ingestion (p < 0.01). With mixed meal, glucose (8.2 ± 0.6 mM/L), insulin (65 ± 12 mU/L) and glucagon (48% ± 7%) responses were lesser than rises following glucose ingestion (p < 0.05) and hypoglycemia did not occur. Conclusion: In IRH, initial hyperglycemia on glucose ingestion may be exacerbated by paradoxical glucagon rise and hypoglycemia may be induced by increased insulin and declining glucagon responses. Resolution of hypoglycemia with high protein low carbohydrate diet may be attributed to blunting of insulin response and concurrent glucagon rise.
基金supported by National Natural Science Founda on of China (70533010)NIH grant # 5R24 TW 007988the Fogarty Interna onal Clinical Research Scholars Support Center at Vanderbilt-AAMC
文摘Objective To describe the distribution of plasma high sensitivity C-reactive protein (hsCRP) and explore the relationship between hsCRP and metabolic risk factors among residents living in longevity areas of China. Methods 268 individuals aged between 40 and 59 years and 506 individuals aged over 90 years were selected from 5 longevity areas of China to participate in a cross section longitudinal cohort study. The participants were interviewed with general health related questionnaire to collect their demographic, behavioral and lifestyle data, as well as their chronic conditions, and meanwhile their physical and biomedical parameters including waist circumference (WC), blood pressure (BP), hsCRP, plasma lipids, and fasting blood glucose (FBG) were measured. Results The median of hsCRP was 0.99 mg/L in the middle-aged group and 2.76 mg/L in the oldest old group. No significant gender difference was observed between the above two groups. Among the oldest old individuals, 36.56% had an hsCRP level 〉3.0 mg/L. The prevalence of high hsCRP was 26.79% in the middle-aged group. The results of stepwise multiple linear regression analyses showed that HDL-C was independently associated with In (hsCRP) concentration in the middle-aged group, whereas In (TG), HDL-C and FBG were correlated after adjustment for gender, study site, smoking, drinking, education and BMI in the oldest old group. Conclusion HDL-C is a stronger predictor of elevated hsCRP than other metabolic factors in the middle-aged population. For the oldest old persons, high TG, low HDL-C, and FBG predict elevated plasma hsCRP.
文摘Objective:To explore the application value of neutrophil/lymphocyte ratio (NLR) combined with high sensitive C reactive protein (hs-CRP) in the evaluation of community acquired pneumonia (CAP). Methods:From November 2015 to October 2016, 58 cases of CAP patients admitted in our department were selected as research objects and were divided into low risk group and high risk group according to the PSI score and CURB-65 standard for evaluation. They were divided into improved group (48 cases) and death group (10 cases) according to prognosis. Hs-CRP was determined by immunoturbidimetric assay, procalcitonin (PCT) by immunofluorescence, NLR by count method of laser scattering, and white blood (WBC) was counted. The differences in WBC, PCT, NLR and hs-CRP between different risk groups were compared, and the correlation was evaluated using Spearman's rank correlation analysis method. The changes in indexes were observed in the improved and death cases. Results:The high risk group had higher NLR, PCT and hs-CRP than low risk group (P<0.05), while no significant difference was found in WBC (P>0.05). No correlation was found between NLR and WBC, while a strong correlation was found between hs-CRP and PCT. The WBC, PCT, NLR and hs-CRP levels were significantly lower in the improved group than the death group (P<0.05). Conclusions:NLR combined with hs-CRP, WBC, and PCT has a good assessment of the severity of CAR, and high levels of NLR, hs-CRP, WBC, and PCT predict the severity of the disease and poor prognosis.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.