To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as...To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.展开更多
Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Method...Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrombopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n=50) treated with adrenosin, vitamins C, K and P, both for 6 months. The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰb/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅡb, GP Ⅲa and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89. 8% in TCM group and 54. 0% in the WM group (x2=45.83, P<0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (x2=62.06, P<0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P>0.05) and higher than those in the WM group (P<0.05). Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰb/Ⅸ, GPⅡ b/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin at the level of receptor protein.展开更多
To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （1...To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.展开更多
Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction （MI） in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same rac...Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction （MI） in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same race. An allele-specific polymerase chain reaction （PCR） was used for genotyping of C807T polymorphism. Results An apparent association was found between the T807 allele and MI among individuals younger than the mean age of 60 years （odds ratio, 2. 49 ; 95 % confidence interval, 1.08 - 6.22 ）. The T807 allele remained an independent risk factor for MI when age, sex, smoking, hypertension, diabetes, bodymass index, LDL-cholesterol and HDL-cholesterol were adjusted by logistic regression. Conclusions GPIa T807 appears to be an independent risk factor for MI.展开更多
The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4...The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.展开更多
OBJECTIVE: To explore platelet activation and the protective effect of aprotinin in patients with hepatolithiasis. METHODS: The count of plaletets and levels of CD_(62P) and CD_(63) were measured by flow cytometry in ...OBJECTIVE: To explore platelet activation and the protective effect of aprotinin in patients with hepatolithiasis. METHODS: The count of plaletets and levels of CD_(62P) and CD_(63) were measured by flow cytometry in 38 patients with hepatolithiasis. Several measurements were carried out after treatment with aprotinin. RESULTS: The levels of CD_(62P), CD_(63) in patients with hepalolithiasis were higher than those in patients with cholecystolithiasis (P<0.05), but the count of platelets was lower (P<0.05). After operation, the levels of CD_(62P), CD_(63) were significantly increased in patients with hepatolithiasis, but the count of platelets was lower (P<0.05). Postoperative levels of CD_(62P), CD_(63) were significantly lower in patients treated with aprotinin than in normal controls (P<0.05); but there was no significant change in the count of platelets in the two groups. CONCLUSION: Platelet activation occurs in patients with hepatolithiasis, and may be inhibited by aprotinin.展开更多
OBJECTIVE Salvia miltiorrhiza bunge contains various active constituents,some of which have been developed as commercially available medicine.Moreover,some other ingredients in Salvia miltiorrhiza play great roles in ...OBJECTIVE Salvia miltiorrhiza bunge contains various active constituents,some of which have been developed as commercially available medicine.Moreover,some other ingredients in Salvia miltiorrhiza play great roles in anti-platelet activity.The aim of the present study was to investigate the effects and the underlying mechanism of miltirone,a lipophilic compound of Salvia miltiorrhiza Bunge.METHODS The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments.Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer.Clot retraction and spreading were imaged by digital camera and fl uorescence microscope.Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone effect in vivo.To elucidate the mechanisms of anti-platelet activity of miltirone,flow cytometry and Western blotting were performed.RESULTS Miltirone(2,4,8 μmol·L^(-1)) was shown to suppress platelet aggregation,dense granule and α granule secretion in a dose-dependent manner.Meanwhile,miltirone inhibited the clot retraction and spreading of washed platelets.It reduced the phosphorylation of PLCγ2,PKC,Akt,GSK3β and ERK1/2 in the downstream signal pathway of collagen receptor.It also reduced the phosphorylation of Src and FAK in the integrin αⅡbβ3 mediated "outside-in" signaling,while it did not suppress the phosphorylation of β3.In addition,miltirone prolonged the occlusion time and reduced collagen/epinephrine induced pulmonary thrombi.CONCLUSION Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2,PI3K/Akt and Src/FAK signaling.Therefore,miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.展开更多
基金supported by a grant from the National Natural Science Foundation of China (No. 30572441).
文摘To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.
文摘Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrombopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n=50) treated with adrenosin, vitamins C, K and P, both for 6 months. The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰb/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅡb, GP Ⅲa and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89. 8% in TCM group and 54. 0% in the WM group (x2=45.83, P<0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (x2=62.06, P<0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P>0.05) and higher than those in the WM group (P<0.05). Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰb/Ⅸ, GPⅡ b/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin at the level of receptor protein.
文摘To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.
文摘Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction （MI） in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same race. An allele-specific polymerase chain reaction （PCR） was used for genotyping of C807T polymorphism. Results An apparent association was found between the T807 allele and MI among individuals younger than the mean age of 60 years （odds ratio, 2. 49 ; 95 % confidence interval, 1.08 - 6.22 ）. The T807 allele remained an independent risk factor for MI when age, sex, smoking, hypertension, diabetes, bodymass index, LDL-cholesterol and HDL-cholesterol were adjusted by logistic regression. Conclusions GPIa T807 appears to be an independent risk factor for MI.
文摘The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.
文摘OBJECTIVE: To explore platelet activation and the protective effect of aprotinin in patients with hepatolithiasis. METHODS: The count of plaletets and levels of CD_(62P) and CD_(63) were measured by flow cytometry in 38 patients with hepatolithiasis. Several measurements were carried out after treatment with aprotinin. RESULTS: The levels of CD_(62P), CD_(63) in patients with hepalolithiasis were higher than those in patients with cholecystolithiasis (P<0.05), but the count of platelets was lower (P<0.05). After operation, the levels of CD_(62P), CD_(63) were significantly increased in patients with hepatolithiasis, but the count of platelets was lower (P<0.05). Postoperative levels of CD_(62P), CD_(63) were significantly lower in patients treated with aprotinin than in normal controls (P<0.05); but there was no significant change in the count of platelets in the two groups. CONCLUSION: Platelet activation occurs in patients with hepatolithiasis, and may be inhibited by aprotinin.
基金supported by National Natural Science Fund of China(81273574) Chinese Herb Key Project by Health and Family Planning Commission of Hubei Province
文摘OBJECTIVE Salvia miltiorrhiza bunge contains various active constituents,some of which have been developed as commercially available medicine.Moreover,some other ingredients in Salvia miltiorrhiza play great roles in anti-platelet activity.The aim of the present study was to investigate the effects and the underlying mechanism of miltirone,a lipophilic compound of Salvia miltiorrhiza Bunge.METHODS The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments.Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer.Clot retraction and spreading were imaged by digital camera and fl uorescence microscope.Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone effect in vivo.To elucidate the mechanisms of anti-platelet activity of miltirone,flow cytometry and Western blotting were performed.RESULTS Miltirone(2,4,8 μmol·L^(-1)) was shown to suppress platelet aggregation,dense granule and α granule secretion in a dose-dependent manner.Meanwhile,miltirone inhibited the clot retraction and spreading of washed platelets.It reduced the phosphorylation of PLCγ2,PKC,Akt,GSK3β and ERK1/2 in the downstream signal pathway of collagen receptor.It also reduced the phosphorylation of Src and FAK in the integrin αⅡbβ3 mediated "outside-in" signaling,while it did not suppress the phosphorylation of β3.In addition,miltirone prolonged the occlusion time and reduced collagen/epinephrine induced pulmonary thrombi.CONCLUSION Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2,PI3K/Akt and Src/FAK signaling.Therefore,miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.
