阿托伐他汀对早期慢性肾脏病伴颈动脉斑块患者外周血淋巴细胞基质金属蛋白酶血管性假血友病因子的作用

doi:10.3877/cma.j.issn.2095-655X.2020.04.004

中华诊断学电子杂志 ›› 2020, Vol. 08 ›› Issue (04) : 231 -236. doi: 10.3877/cma.j.issn.2095-655X.2020.04.004

所属专题：文献；

临床研究

阿托伐他汀对早期慢性肾脏病伴颈动脉斑块患者外周血淋巴细胞基质金属蛋白酶血管性假血友病因子的作用

曲忠森¹^,^†(

), 潘永超², 张清德³

^1. 201306　上海健康医学院附属第六人民医院东院康复科
^2. 201306　上海健康医学院附属第六人民医院神经内科
^3. 274031　菏泽市立医院泌尿内科

收稿日期:2019-12-02 出版日期:2020-11-26
通信作者: 曲忠森
基金资助:
山东省医药卫生科技发展计划项目(2016WS0098); 上海健康医学院2018年度种子基金课题(SFP-18-22-14-004)

Effects of atorvastatin on MMPs and vWF in peripheral blood lymphocytes in patients of early chronic kidney disease with carotid artery plaque

Zhongsen Qu¹^,^†(), Yongchao Pan², Qingde Zhang³

^1. Department of Rehabilitation, the Sixth People′s Hospital Affiliated to Shanghai Health Medical College, Shanghai 201306, China
^2. Department of Neurology, the Sixth People′s Hospital Affiliated to Shanghai Health Medical College, Shanghai 201306, China
^3. Department of Urology, Heze Municipal Hospital, Heze 274031, China

Received:2019-12-02 Published:2020-11-26
Corresponding author: Zhongsen Qu
About author:
Corresponding author: Qu Zhongsen, Email: quzhongsen@163.com

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引用本文：

曲忠森, 潘永超, 张清德. 阿托伐他汀对早期慢性肾脏病伴颈动脉斑块患者外周血淋巴细胞基质金属蛋白酶血管性假血友病因子的作用[J/OL]. 中华诊断学电子杂志, 2020, 08(04): 231-236.

Zhongsen Qu, Yongchao Pan, Qingde Zhang. Effects of atorvastatin on MMPs and vWF in peripheral blood lymphocytes in patients of early chronic kidney disease with carotid artery plaque[J/OL]. Chinese Journal of Diagnostics(Electronic Edition), 2020, 08(04): 231-236.

目的

探讨阿托伐他汀对早期慢性肾脏病(CKD)伴有颈动脉斑块患者周围血淋巴细胞基质金属蛋白酶(MMPs)、血管性假血友病因子(vWF)的作用。

方法

选取2017年1月至10月上海市第六人民医院东院和菏泽市立医院肾脏科就诊的143例CKD 1～2期并颈动脉斑块患者，按随机数字表法分为CKD组(n＝76)和治疗组(n＝67)，并选择同期健康体检正常者50例作为对照组，治疗组口服阿托伐他汀。治疗6个月后比较3组患者血脂水平和颈动脉内膜中层厚度(IMT)，并比较3组患者治疗第1，2，3，6个月后外周血淋巴细胞MMP-2、MMP-9及vWF水平的变化。

结果

与对照组比较，CKD组和治疗组在治疗第6个月后甘油三酯[(1.42±0.40)mmol/L，(3.58±0.78)mmol/L，(1.78±0.46)mmol/L]、总胆固醇[(4.56±0.78)mmol/L，(6.88±1.39)mmol/L，(5.16±1.14)mmol/L]水平、IMT[(0.78±0.23)mm，(1.56±0.43)mm，(1.06±0.22)mm]和外周血淋巴细胞MMP-9[(124.10±42.96)μg/L，(232.82±90.16)μg/L，(158.57±57.14) μg/L]、MMP-2[(141.09±44.98)μg/L，(262.82±110.98)μg/L，(154.48±56.86)μg/L]及vWF水平[(111.68±42.29)μg/L，(276.82±111.68)μg/L，(142.32±46.44)μg/L]明显升高，均差异有统计学意义(F＝5.90，4.28，3.45，11.34，12.45，12.35，均P<0.05)，但治疗组甘油三酯、总胆固醇、IMT、MMP-9、MMP-2和vWF水平与CKD组比较均降低，均差异有统计学意义(t＝4.21，1.22，5.13，4.90，5.90，10.00，均P<0.05)。

结论

阿托伐他汀可能通过降低早期CKD伴颈动脉斑块患者外周血淋巴细胞MMP-2、MMP-9和vWF水平，起到稳定斑块的作用。

关键词: 阿托伐他汀, 慢性肾脏病, 淋巴细胞, 基质金属蛋白酶, 血管性假血友病因子

Objective

To explore the effects of atorvastatin on matrix metalloproteinase (MMPs) and von Willebrand factor (vWF) in peripheral blood lymphocytes in patients of early chronic kidney disease (CKD) with carotid artery plaque.

Methods

From January to October 2017, 143 patients with stage 1-2 CKD and carotid artery plaque who visited the Kidney Department of the East Hospital of Shanghai Sixth People′s Hospital and Heze Municipal Hospital were selected. According to the random number table method, they were divided into the CKD group (n=76) and the treatment group (n=67), and 50 healthy people with normal physical examination in the corresponding period were selected as the control group. The treatment group was treated with atorvastatin for oral administration. After 6 months of treatment, blood lipid level and carotid intima-media thickness (IMT) of the 3 groups were compared, and the changes of MMP-2, MMP-9 and vWF levels of peripheral blood lymphocytes in the 3 groups were compared after 1, 2, 3 and 6 months of treatment.

Results

Compared to the control group, after 6 months of treatment, the triglycerides levels [(1.42±0.40)mmol/L, (3.58±0.78)mmol/L, (1.78±0.46)mmol/L], total cholesterol levels [(4.56±0.78)mmol/L, (6.88±1.39)mmol/L, (5.16±1.14)mmol/L], IMT levels [(0.78±0.23)mm, (1.56±0.43)mm, (1.06±0.22)mm] and peripheral blood lymphocytes of MMP-9 levels [(124.10±42.96)μg/L, (232.82±90.16)μg/L, (158.57±57.14)μg/L], MMP-2 levels [(141.09±44.98)μg/L, (262.82±110.98)μg/L, (154.48±56.86)μg/L] and vWF levels [(111.68±42.29)μg/L, (276.82±111.68)μg/L, (142.32±46.44)μg/L] in the CKD group and treatment group were significantly increased, with statistically significant differences (F=5.90, 4.28, 3.45, 11.34, 12.45, 12.35, all P<0.05). The levels of triglyceride, total cholesterol, IMT, MMP-9, MMP-2 and vWF levels in the treatment group were lower than those in the CKD group, all the differences were statistically significant (t=4.21, 1.22, 5.13, 4.90, 5.90, 10.00, all P<0.05).

Conclusions

In early CKD patients with carotid artery plaque, atorvastatin may play a role in stabilizing plaques by reducing MMP-2, MMP-9 and vWF levels in peripheral blood lymphocytes.

Key words: Atorvastatin, Chronic kidney disease, Lymphocyte, Matrix metalloproteinase, Von Willebrand factor

表1 早期CKD并颈动脉斑块患者与健康体检者临床基本情况比较

组别	例数	性别(例，男/女)	年龄(岁，±s)	血糖(mmol/L，±s)	总胆固醇(mmol/L，±s)	甘油三酯(mmol/L，±s)	IMT(mm，±s)	收缩压(mmHg，±s)	舒张压(mmHg，±s)	血清肌酐(μmol/L，±s)
对照组	50	27/23	47.66±6.12	5.36±0.47	4.13±0.82	1.58±0.32	0.71±0.13	124.82±14.61	78.64±8.84	85.56±37.52
CKD组	76	49/27	52.42±5.83	7.67±1.84^a	7.24±1.46^a	2.43±0.49^a	1.42±0.32^a	168.29±23.42^a	98.45±11.60^a	115.32±23.78^a
治疗组	67	41/26	54.60±4.82	7.34±1.66^a	6.94±1.27^a	2.89±0.57^a	1.36±0.27^a	161.40±22.56 ^a	92.78±10.70^a	111.99±27.22^a
统计量	?	χ²＝9.34	F＝7.07	F＝2.25	F＝2.97	F＝2.55	F＝0.58	F＝1.17	F＝0.87	F＝5.13
P值	?	0.90	0.54	0.04	0.04	0.03	0.00	0.02	0.00	0.00

表1 早期CKD并颈动脉斑块患者与健康体检者临床基本情况比较

组别	例数	性别(例，男/女)	年龄(岁，±s)	血糖(mmol/L，±s)	总胆固醇(mmol/L，±s)	甘油三酯(mmol/L，±s)	IMT(mm，±s)	收缩压(mmHg，±s)	舒张压(mmHg，±s)	血清肌酐(μmol/L，±s)
对照组	50	27/23	47.66±6.12	5.36±0.47	4.13±0.82	1.58±0.32	0.71±0.13	124.82±14.61	78.64±8.84	85.56±37.52
CKD组	76	49/27	52.42±5.83	7.67±1.84^a	7.24±1.46^a	2.43±0.49^a	1.42±0.32^a	168.29±23.42^a	98.45±11.60^a	115.32±23.78^a
治疗组	67	41/26	54.60±4.82	7.34±1.66^a	6.94±1.27^a	2.89±0.57^a	1.36±0.27^a	161.40±22.56 ^a	92.78±10.70^a	111.99±27.22^a
统计量	?	χ²＝9.34	F＝7.07	F＝2.25	F＝2.97	F＝2.55	F＝0.58	F＝1.17	F＝0.87	F＝5.13
P值	?	0.90	0.54	0.04	0.04	0.03	0.00	0.02	0.00	0.00

表2 3组人群阿托伐他汀治疗6个月后血脂水平和IMT比较(±s)

组别	例数	总胆固醇(mmol/L)	甘油三酯(mmol/L)	IMT(mm)
对照组	50	4.56±0.78	1.42±0.40	0.78±0.23
CKD组	76	6.88±1.39^a	3.58±0.78^a	1.56±0.43^a
治疗组	67	5.16±1.14^bc	1.78±0.46^c	1.06±0.22^c
F值	?	4.28	5.90	3.45
P值	?	0.03	0.00	0.03

表2 3组人群阿托伐他汀治疗6个月后血脂水平和IMT比较(±s)

组别	例数	总胆固醇(mmol/L)	甘油三酯(mmol/L)	IMT(mm)
对照组	50	4.56±0.78	1.42±0.40	0.78±0.23
CKD组	76	6.88±1.39^a	3.58±0.78^a	1.56±0.43^a
治疗组	67	5.16±1.14^bc	1.78±0.46^c	1.06±0.22^c
F值	?	4.28	5.90	3.45
P值	?	0.03	0.00	0.03

表3 3组人群阿托伐他汀治疗前后外周血淋巴细胞MMP-9水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	126.47±40.94	132.46±44.51	128.68±39.28	131.52±46.32	124.10±42.96
CKD组	76	216.36±72.48^a	208.54±63.78^a	213.54±78.24^a	229.58±84.78^a	232.82±90.16^a
治疗组	67	229.14±80.56^b	192.46±70.21^b	176.48±68.31^bc	168.59±61.38^bc	158.57±57.14^bc
F值	?	9.93	9.00	9.42	10.63	11.34
P值	?	0.04	0.04	0.04	0.02	0.02

表3 3组人群阿托伐他汀治疗前后外周血淋巴细胞MMP-9水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	126.47±40.94	132.46±44.51	128.68±39.28	131.52±46.32	124.10±42.96
CKD组	76	216.36±72.48^a	208.54±63.78^a	213.54±78.24^a	229.58±84.78^a	232.82±90.16^a
治疗组	67	229.14±80.56^b	192.46±70.21^b	176.48±68.31^bc	168.59±61.38^bc	158.57±57.14^bc
F值	?	9.93	9.00	9.42	10.63	11.34
P值	?	0.04	0.04	0.04	0.02	0.02

表4 3组人群阿托伐他汀治疗前后外周血淋巴细胞MMP-2水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	134.64±46.32	128.66±39.76	132.22±49.19	138.79±41.87	141.09±44.98
CKD组	76	230.92±104.23^a	238.77±103.58^a	248.54±108.62^a	245.71±98.39^a	262.82±110.98^a
治疗组	67	242.25±94.57^b	216.73±74.45^b	186.94±72.36^bc	178.85±76.34^bc	154.48±56.86^c
F值	?	8.63	8.99	10.84	10.67	12.45
P值	?	0.03	0.03	0.02	0.02	0.02

表4 3组人群阿托伐他汀治疗前后外周血淋巴细胞MMP-2水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	134.64±46.32	128.66±39.76	132.22±49.19	138.79±41.87	141.09±44.98
CKD组	76	230.92±104.23^a	238.77±103.58^a	248.54±108.62^a	245.71±98.39^a	262.82±110.98^a
治疗组	67	242.25±94.57^b	216.73±74.45^b	186.94±72.36^bc	178.85±76.34^bc	154.48±56.86^c
F值	?	8.63	8.99	10.84	10.67	12.45
P值	?	0.03	0.03	0.02	0.02	0.02

表5 3组人群阿托伐他汀治疗前后外周血淋巴细胞vWF水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	98.76±36.51	102.82±38.24	95.79±29.97	108.45±37.88	111.68±42.29
CKD组	76	236.18±89.58^a	242.65±91.70^a	248.54±98.62^a	268.46±106.36^a	276.82±111.68^a
治疗组	67	228.94±84.37^b	204.91±78.94^bc	192.84±74.43^bc	169.86±66.35^bc	142.32±46.44^bc
F值	?	15.23	10.89	12.36	12.73	12.35
P值	?	0.01	0.02	0.02	0.02	0.02

表5 3组人群阿托伐他汀治疗前后外周血淋巴细胞vWF水平的变化(μg/L，±s)

组别	例数	治疗前	治疗第1个月后	治疗第2个月后	治疗第3个月后	治疗第6个月后
对照组	50	98.76±36.51	102.82±38.24	95.79±29.97	108.45±37.88	111.68±42.29
CKD组	76	236.18±89.58^a	242.65±91.70^a	248.54±98.62^a	268.46±106.36^a	276.82±111.68^a
治疗组	67	228.94±84.37^b	204.91±78.94^bc	192.84±74.43^bc	169.86±66.35^bc	142.32±46.44^bc
F值	?	15.23	10.89	12.36	12.73	12.35
P值	?	0.01	0.02	0.02	0.02	0.02

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Effects of atorvastatin on MMPs and vWF in peripheral blood lymphocytes in patients of early chronic kidney disease with carotid artery plaque

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Effects of atorvastatin on MMPs and vWF in peripheral blood lymphocytes in patients of early chronic kidney disease with carotid artery plaque