藏红花素对自发性高血压大鼠血管内皮功能障碍及动脉粥样硬化的作用及其ROCK/JNK信号通路机制

doi:10.13481/j.1671-587X.20220614

Abstract

Abstract:

Methods Ten Wistar Kyoto rats were selected as normal group， and 40 SH rats were randomly divided into model group and low （25 mg·kg^－1·d^－1）， medium （50 mg·kg^－1·d^－1）， and high doses of CR （100 mg·kg^－1·d^－1） groups， and there were 10 rats in each group. The rats in normal group and model group were intraperitoneally injected with the same amount of normal saline. After administration， the blood pressure， blood lipid levels，atherosclerosis index （AI）， 24 h urine 8-iso-prostaglandin F2α （8-iso-PGF2α） renal excretion of the rats in various groups were detected； HE staining was used to observe the morphology of aorta tissue of the rats in various groups；the serum activities of glutathione peroxidase （GSH-Px） and the serum levels of malondialdehyde （MDA）， nitric oxide （NO）， endothelin-1 （ET-1），and thromboxane B2 （TXB2） of the rats in various groups were detected by ELISA method；the expression levels of RhoA/ RhoA/Rho related kinase 1 （ROCK1）， ROCK2 and C-Jun amino acid terminal kinase （JNK） mRNA in aorta tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） method；Western blotting mehod was used to detect the expression levels of ROCK1， ROCK2， JNK，and phophorylated JNK（p-JNK） proteins in aorta tissue of the rats in various groups. Results Compared with normal group， the systolic blood pressure and diastolic blood pressure， 24 h urine 8-iso-PGF2α renal excretion， levels of serum total cholesterol（TC），triglyceride（TG） and low density lipoprotein cholesterol（LDL-c）， AI，levels of MDA， ET-1 and TXB2， expression levels of ROCK1， ROCK2， and JNK mRNA， expression levels of ROCK1， ROCK2， JNK， and p-JNK proteins in aorta tissue of the rats in model group were increased （P<0.05），the serum acitivity of GSH-Px and serum levels of high density lipoprotein cholesterol（HDL-c） and NO were decreased （P<0.05）. In model group， the aortic wall was rough and thickened， and a large number of foam cells and atherosclerotic necrosis substances were distributed. Compared with model group， the systolic blood pressure and diastolic blood pressure，24 h urine 8-iso-PGF2α renal excretion， serum levels of TC， TG，and LDL-c， AI， levels of MDA， ET-1，and TXB2， expression levels of ROCK1， ROCK2 and JNK mRNA，expression levels of ROCK1， ROCK2， JNK， and p-JNK proteins in aorta tissue of the rats in low， medium， and high doses of CR groups were decreased （P<0.05）， and the serum activity of GSH-Px and serum levels of HDL-c and NO were increased （P<0.05）. In low dose of CR group， the roughness and thickening of the aortic wall and the distribution of the foam cells and atherosclerotic necrosis substances in the aorta tissue were decreased to varying degrees.Compared with low dose of CR group， the systolic blood pressure and diastolic blood pressure，24 h urine 8-iso-PGF2α renal excretion， serum levels of TC， TG， and LDL-c， AI， levels of MDA， ET-1， and TXB2，expression levels of ROCK1， ROCK2 and JNK mRNA in aora tissue， expression levels of ROCK1， ROCK2， JNK， and p-JNK proteins in aorta tissue of the rats in medium dose of CR group were decreased （P<0.05）， while the serum activity of GSH-Px and serum levels of HDL-c and NO were increased （P<0.05）. In medium dose of CR group， the roughness and thickening of the aortic wall and the distribution of the foam cells and atherosclerotic necrosis substances in the aorta tissue were reduced. Compared with medium dose of CR group，the systolic blood pressure and diastolic blood pressure， 24 h urine 8-iso-PGF2α renal excretion， serum levels of TC， TG， and LDL-c， AI， levels of MDA， ET-1， and TXB2， expression levels of ROCK1， ROCK2，JNK mRNA in aorta tissue， expression levels of ROCK1， ROCK2， JNK， and p-JNK proteins in aorta tissue of the rats in high dose of CR group were decreased （P<0.05）， while the serum activity of GSH-Px and serum levels of HDL-c and NO were increased （P<0.05）. The atherosclerotic pathomorphology of aorta wall of the rats in high dose of CR group was significantly improved. Conclusion CR can improve ED and As in the SH rats， and its mechanism may be related to inhibiting the activation of ROCK/JNK signaling pathway. Objective To investigate the effect of crocin （CR） on vascular endothelial dysfunction （ED） and atherosclerosis （As） in the rats with spontaneously hypertension （SH），and to clarify its possible mechanism.

Key words: Crocin, Spontaneous hypertension, Vascular endothelial dysfunction, Atherosclerosis, Rho protein kinase, C-jun amino acid terminal kinase

CLC Number:

R544.1

Shuhua YU,Wei LIU,Qianqian WU,Dongwei YANG. Effect of crocetin on vascular endothelial dysfunction and atherosclerosis in spontaneously hypertensive rats and its ROCK/JNK signaling pathway mechanism[J].Journal of Jilin University(Medicine Edition), 2022, 48(6): 1481-1489.

Figures/Tables 7

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References 27

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Group	Systolic blood pressure	Diastolic blood pressure
Normal	113.35±4.26	72.27±4.25
Model	187.68±12.03^*	116.91±5.27^*
CR Low dose	168.76±10.03^△	108.17±4.63^△
Medium dose	137.93±8.11^△＃	97.25±5.91^△＃
High dose	124.22±6.74^△＃○	82.78±4.02^△＃○

Group	TC[c_B/（mmol·L^－1)]	TG[c_B/（mmol·L^－1)]	LDL-c[c_B/（mmol·L^－1)]	HDL-c[c_B/（mmol·L^－1)]	AI
Normal	1.08±0.11	0.62±0.06	0.76±0.05	0.94±0.08	0.13±0.03
Model	2.25±0.16^*	1.48±0.09^*	2.33±0.15^*	0.44±0.05^*	4.08±0.57^*
CR Low dose	2.07±0.12^△	1.36±0.06^△	2.18±0.08^△	0.52±0.03^△	2.87±0.39^△
Medium dose	1.78±0.10^△＃	1.14±0.06^△＃	1.77±0.09^△＃	0.68±0.04^△＃	1.59±0.18^△＃
High dose	1.42±0.09^△＃○	0.85±0.06^△＃○	1.32±0.10^△＃○	0.87±0.04^△＃○	0.62±0.09^△＃○

Group	MDA[c_B/(nmol·L^－1）]	GSH-Px[c_B/(μmol·L^－1）]	NO[c_B/(μmol·L^－1）]	ET-1 [ρ_B/(ng·L^－1）]	TXB2[ρ_B/(ng·L^－1）]
Normal	8.12±0.21	109.52±9.68	22.10±2.18	65.85±4.31	32.61±3.10
Model	15.27±1.08^*	58.24±3.68^*	13.58±0.72^*	114.78±5.95^*	58.99±4.60^*
CR Low dose	14.12±0.62^△	65.09±4.03^△	14.54±1.10^△	103.70±5.64^△	53.33±3.77^△
Medium dose	11.86±0.84^△＃	78.39±6.20^△＃	16.66±1.14^△＃	87.86±6.96^△＃	46.06±3.69^△＃
High dose	9.52±0.81^△＃○	98.67±7.51^△＃○	19.96±0.94^△＃○	72.46±4.69^△＃○	35.86±3.24^△＃○

Group	ROCK1	ROCK2	JNK
Normal	1.00±0.01	1.01±0.01	1.02±0.01
Model	5.87±0.54^*	4.88±0.59^*	4.72±0.54^*
CR Low dose	5.26±0.32^＃	3.95±0.24^＃	4.11±0.26^＃
Medium dose	3.94±0.47^△＃	2.89±0.21^△＃	2.77±0.15^△＃
High dose	1.96±0.18^△＃○	1.71±0.34^△＃○	1.62±0.26^△＃○

Group	ROCK1	ROCK2	JNK	p-JNK
Normal	0.09±0.02	0.18±0.03	0.38±0.03	0.16±0.02
Model	0.64±0.05^*	0.65±0.05^*	0.92±0.04^*	0.53±0.05^*
CR Low dose	0.54±0.05^＃	0.57±0.03^＃	0.86±0.04^＃	0.42±0.05^＃
Medium dose	0.38±0.05^△＃	0.41±0.02^△＃	0.79±0.04^△＃	0.37±0.03^△＃
High dose	0.19±0.03^△＃○	0.24±0.04^△＃○	0.58±0.04^△＃○	0.31±0.03^△＃○

Effect of crocetin on vascular endothelial dysfunction and atherosclerosis in spontaneously hypertensive rats and its ROCK/JNK signaling pathway mechanism

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