1. 山东中医药大学第一临床医学院
2. 山东中医药大学附属医院
纸质出版:2017
移动端阅览
[1]郭金昊,姜月华,杨传华,王震.蒺藜超微粉对血管紧张素Ⅱ诱导的下丘脑神经元细胞损伤IKK-β/NF-κB信号通路的影响[J].中医杂志,2017,58(02):151-156.
GUO Jinhao, JIANG Yuehua, YANG Chuanhua, et al. Effects of Jili [Tribulus terrestris L. 蒺藜] on IKK-β/NF-κB Signaling Pathway in Hypothalamic Neuron Injury Induced by Angiotensin Ⅱ[J]. Journal of Traditional Chinese Medicine2017, 58(2): 151-156.
[1]郭金昊,姜月华,杨传华,王震.蒺藜超微粉对血管紧张素Ⅱ诱导的下丘脑神经元细胞损伤IKK-β/NF-κB信号通路的影响[J].中医杂志,2017,58(02):151-156. DOI: 10.13288/j.11-2166/r.2017.02.015.
GUO Jinhao, JIANG Yuehua, YANG Chuanhua, et al. Effects of Jili [Tribulus terrestris L. 蒺藜] on IKK-β/NF-κB Signaling Pathway in Hypothalamic Neuron Injury Induced by Angiotensin Ⅱ[J]. Journal of Traditional Chinese Medicine2017, 58(2): 151-156. DOI: 10.13288/j.11-2166/r.2017.02.015.
目的探讨蒺藜治疗高血压病的可能作用机制。方法体外原代培养Wistar乳鼠下丘脑神经元细胞
并以血管紧张素Ⅱ(AngⅡ)诱导细胞损伤即高血压细胞模型。药效学观察时细胞分为5组
模型组(2×10-6mol/L AngⅡ)、蒺藜低剂量组(3μg/ml蒺藜预孵育2 h后加入2×10-6mol/L AngⅡ)、蒺藜高剂量组(30μg/ml蒺藜预孵育2 h后加入2×10-6mol/L AngⅡ)、缬沙坦组(10-5mol/L缬沙坦预孵育2 h后加入2×10-6mol/L AngⅡ)、正常组(无任何干预)
分别于AngⅡ作用24、48、72 h时检测各组细胞绝对数量、神经元轴突长度、胞体面积、存活率、凋亡率
并于72 h时检测细胞因子IKK-α、IKK-β、NF-κB p65、IκBα、JAK2、STAT3、AT1、GnRH、PKC、PI3K的mRNA表达;药理学观察时细胞分为6组
模型组(2×10-6mol/L AngⅡ)、蒺藜组(30μg/ml蒺藜预孵育2 h后加入2×10-6mol/L AngⅡ)、缬沙坦组(10-5mol/L缬沙坦预孵育2 h后加入2×10-6mol/L AngⅡ)、拮抗剂组(20μmol/L TPCA-1预孵育2 h后加入2×10-6mol/L AngⅡ)、蒺藜+拮抗剂组(30μg/ml蒺藜+20μmol/L TPCA-1预孵育2 h后加入2×10-6mol/L AngⅡ)、正常组(无任何干预)
根据药效学观察结果确定AngⅡ作用时间及相关细胞因子
并检测各组细胞相关因子mRNA及蛋白的表达。结果与正常组比较
模型组从AngⅡ干预24 h开始的各时间点细胞绝对数量、胞体面积、存活率、凋亡率均显著升高
神经元轴突长度显著降低;与模型组比较
蒺藜高剂量组、缬沙坦组各时间点细胞绝对数量、胞体面积、存活率、凋亡率均显著下降
神经元轴突长度增加(P<0.05)。与正常组比较
模型组IKK-β、NF-κB p65、JAK2、STAT3、AT1、GnRH、PKC、PI3K表达显著上调
IKK-α、IKBα表达显著下调(P<0.05)。与模型组比较
蒺藜高剂量组IKK-β、NF-κB p65、JAK2、AT1、GnRH、PKC表达下降
IKK-α、IκBα表达升高;蒺藜低剂量组IKK-β、NF-κB p65、AT1、PKC表达下降
IKK-α、IκBα表达升高;缬沙坦组IKK-β、NF-κB p65、AT1、GnRH、PKC表达下降
IKK-α、IκBα表达上调(P<0.05)。根据以上结果确定药理学观察时AngⅡ干预时间为24 h
相关细胞因子为IκBα、IKK-β、NF-κB p65、NF-κB p50。与正常组比较
模型组下丘脑神经元细胞IKK-β、NF-κB p50、NF-κB p65mRNA和蛋白表达上调
IκBα表达下调;与模型组比较
缬沙坦组和蒺藜组NF-κB p50、NF-κB p65、IKK-β的表达下调
IκBα表达上调;与缬沙坦组比较
蒺藜组NF-κB p65、IKK-β表达下调
IκBα表达上调(P<0.05)。结论蒺藜可有效维持血压调节中枢功能
其降压机制可能与调节下丘脑IKK-β/NF-κB信号通路活性有关。
Objective To explore the potential mechanism of Jili [Tribulus terrestris L. 蒺藜]in the treatment of hypertension. Methods The hypertension cell model was induced by angiotensin Ⅱ( Ang Ⅱ) in the primary cultured hypothalamic neurons from neonatal Wistar rats. During the pharmacodynamics observation
the cells were divided into 5 groups: model group( 2 × 10-6mol / L AngⅡ)
low dose Jili group( preincubated with 3 μg / ml Jili for2 hours
then 2 × 10-6mol / L AngⅡ was added)
high dose Jili group( preincubated with 30 μg / ml Jili for 2 hours
then 2 × 10-6mol / L AngⅡ was added)
Valsartan group( preincubated with 10-5mol / L Valsartan for 2 hours
then2 × 10-6mol / L Ang Ⅱ was added) and control group( with no intervention). Then the cell number
the axonal length
the soma area
the survival rate and the apoptosis rate in each group were detected at the 24 th
48th and 72 nd hour after AngⅡ intervention. Also
the mRNA expression level of some cytokines
such as IκBα
IKK-α
IKK-β
NF-κB p65
JAK2
STAT3
AT1
GnRH
PKC and PI3 K
were detected at the 72 nd hour. During the pharmacological observation
the cells were divided into 6 groups: model group( 2 × 10-6mol / L AngⅡ)
Jili group( preincubated with 30 μg / ml Jili for 2 hours
then 2 × 10-6mol / L AngⅡwas added)
Valsartan group( preincubated with 10-5mol / L Valsartan for 2 hours
then 2 × 10-6mol / L Ang Ⅱ was added)
antagonist group( preincubated with 20 μmol / L TPCAK-1 for 2 hours
then 2 × 10-6mol / L AngⅡ was added)
Jili plus antagonist group( preincubated with 30 μg /ml Jili and 20 μmol / L TPCA-1 for 2 hours
then 2 × 10-6mol / L AngⅡ was added) and control group( with no intervention). Then based on the results of pharmacodynamics observation
the action time of AngⅡ and the related cytokines were determined. Also
the expression level of mRNA and protein of related cytokines of each group were detected.Results Compared with those in the control group
the cell number
the soma area
the survival rate and the apoptosis rate in the model group increased significantly
while the axonal length deceased significantly at each time point after 24 hours after AngⅡ intervention; compared with those in the model group
the cell numbers
the soma areas
the survival rates and the apoptosis rates in the high dose Jili group and Valsartan group decreased significantly
while the axonal lengths increased significantly( P < 0. 05). Compared with those in the control group
the expression levels of IKK-β
NF-κB p65
JAK2
STAT3
AT1
GnRH
PKC and PI3 K increased significantly
while the levels of IKK-αand IκBα decreased significantly in the model group( P < 0. 05). Compared with those in the model group
the expression levels of IKK-β
NF-κB p65
JAK2
AT1
GnRH and PKC decreased
and the levels of IKK-α and IκBαincreased in the high does Jili group; the expression levels of IKK-β
NF-κB p65
AT1 and PKC decreased
and the levels of IKK-α and IκBα increased in the low does Jili group; the expression levels of IKK-β
NF-κB p65
AT1
GnRH and PKC decreased
and the levels of IKK-α and IκBα increased in Valsartan group( P < 0. 05). Based on the results above
the intervention time of AngⅡ was determined as 24 h
and the related cytokines were determined as IκBα
IKK-β
NF-κB p65 and NF-κB p50. Compared with those in the control group
the expression levels of the mRNA and the protein of IKK-β
NF-κB p50 and NF-κB p65 increased
while those of IκBα decreased in the model group; compared with those in the model group
the expressions of IKK-β
NF-κB p50 and NF-κB p65 decreased
while the expression of IκBα increased in Valsartan group and Jili group; compared with those in Valsartan group
the expressions of NF-κB p65 and IKK-β decreased
while the expression of IκBα increased in Jili group( P < 0. 05).Conclusion Jili could maintain the function of the blood pressure regulation center
and its potential mechanism of anti-hypertension might be related to regulating the IKK-β / NF-κB signaling pathway in hypothalamic neurons.
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