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浙江大学学报(医学版)  2022, Vol. 51 Issue (4): 422-429    DOI: 10.3724/zdxbyxb-2022-0157
专题报道     
红景天苷对急进高原大鼠肺组织的保护作用
王子晗1,2,郭茜文1,2,马江红1,2,程俊飞2,赵安鹏2,李文斌1,2,王荣1,2,*()
1. 甘肃中医药大学药学院,甘肃 兰州 730000
2. 中国人民解放军联勤保障部队第九四〇医院药剂科 全军高原医学实验室,甘肃 兰州 730050
Protective effect of salidroside on lung tissue in rats exposed rapidly to high altitude
WANG Zihan1,2,GUO Qianwen1,2,MA Jianghong1,2,CHENG Junfei2,ZHAO Anpeng2,LI Wenbin1,2,WANG Rong1,2,*()
1. College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China;
2. Department of Pharmacy, the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Key Laboratory of the Plateau Medicine, Lanzhou 730050, China
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摘要:

目的:研究红景天苷对急进高原大鼠肺组织的保护作用及机制。 方法:Wistar雄性大鼠36只,随机分为空白对照组、模型对照组、红景天胶囊组以及红景天苷小 (14?mg/kg)、中 (28?mg/kg)、大 (56?mg/kg)剂量组,每组6只。除空白对照组外,其他各组预防性灌胃给药5?d后急进海拔 4010?m的高原实地建立低压性缺氧模型,检测大鼠血气指标,酶联免疫吸附试验测定血清炎症因子水平,试剂盒测定肺组织氧化应激指标,苏木精-伊红染色观察肺组织病理学改变,蛋白质印迹法检测肺组织中闭合蛋白的表达量。 结果:与空白对照组比较,模型对照组动脉血氧饱和度(SaO 2)、动脉血氧分压(PaO 2)、血液酸碱度、标准碳酸氢盐(SBC)和实际碳酸氢盐水平显著下降,血红蛋白水平显著上升(均 P<0.05);肥大细胞蛋白酶(MCP)1、白介素(IL)-6和IL-1β含量显著增加,γ干扰素含量显著减少(均P<0.01);肺组织中谷胱甘肽和总超氧化物歧化酶含量显著下降,丙二醛含量显著增加(均P<0.01)。红景天胶囊和红景天苷各剂量组SaO2、血液酸碱度、血红蛋白、SBC和实际碳酸氢盐较模型对照组均有一定改善;炎症因子和氧化应激指标较模型对照组均有不同程度改善,其中红景天苷组MCP-1、IL-6改善情况优于红景天胶囊组。红景天胶囊和红景天苷小、中、大剂量组肺组织缺氧损伤改善,细胞壁逐渐变薄,肺泡壁逐渐完整。模型对照组闭合蛋白含量较空白对照组减少( P<0.05),而红景天苷大剂量组闭合蛋白含量较模型对照组显著增加(P<0.01)。结论:红景天苷可改善大鼠由于缺氧所致的血气指标失调、缺氧症状和酸碱平衡紊乱、炎症因子失调,改善肺组织损伤、氧化应激损伤等,对急进高原大鼠肺组织损伤具有保护作用,且改善效果总体优于红景天胶囊。

关键词: 红景天苷低压性缺氧肺损伤炎症因子氧化应激闭合蛋白大鼠    
Abstract:

Objective: To study the protective effect and mechanism of salidroside on lung tissue of rats exposed rapidly to high altitude. Methods: Thirty-six Wistar male rats were randomly divided into blank control group, model control group, Rhodiola rosea capsule (137?mg/kg) group, salidroside low-dose (14?mg/kg), medium-dose (28?mg/kg) and high-dose (56?mg/kg) groups, with 6 rats in each group. After 5 continuous days of drug administration in the plain lab, rats were rapidly moved to 4010?m plateau field lab. After exposure to hypoxia condition for 3 days the blood gas indexes were detected; the serum levels of inflammatory factors were measured by enzyme linked immunosorbent assay (ELISA); the oxidative stress index of lung tissue was measured; the pathological changes of lung tissue were observed by microscopy with hematoxylin and eosin (HE) staining; and the expression of occludin in lung tissues was determined by western blotting. Results: Compared with blank control group, arterial oxygen saturation (SaO 2), arterial oxygen partial pressure (PaO 2), blood pH, standard bicarbonate (SBC) and actual bicarbonate levels in model control group were significantly decreased, and hemoglobin level was significantly increased (all P<0.05). In the model control group, the contents of mast cell protease (MCP) 1, interleukin (IL)-6 and IL-1β were significantly increased, while the contents of interferon-γ were significantly decreased (allP<0.01). The contents of glutathione and total superoxide dismutase in the lung tissues of model control group were significantly decreased, while the content of malondialdehyde was significantly increased (allP<0.01). AfterRhodiola rosea and salidroside were given, SaO 2, pH, hemoglobin, SBC and actual bicarbonate were improved compared with the model control group. Compared with the model control group, the Rhodiola rosea group and salidroside groups had different degrees of improvement in the contents of the above inflammatory factors and oxidative stress indexes, and the salidroside groups had better improvement in MCP-1 and IL-6 than the Rhodiola rosea group. HE staining showed that, after the administration of Rhodiola rosea capsules and salidroside at low, medium and high doses, the hypoxic injury was significantly improved, the cell wall gradually became thinner, and the alveolar wall gradually became complete. The expression of occludin in the model control group was lower than that in the blank control group ( P<0.05), while the expression of occludin in the salidroside high-dose group was significantly higher than that in the model control group (P<0.01).Conclusion: Salidroside can improve the abnormality of blood gas index, hypoxia symptoms and acid-base balance disorder, dysregulation of inflammatory factors caused by hypoxia in rats, and improve lung tissue injury and oxidative stress injury, which has a protective effect on lung tissue injury of rats exposed rapidly to the high-altitude plateau, and the effect is better than Rhodiola rosea capsule on the whole.

Key words: Salidroside    Hypobaric hypoxia    Lung injury    Inflammatory cytokines    Oxidative stress    Occludin    Rats
收稿日期: 2022-04-14 出版日期: 2022-11-16
CLC:  R965.2  
基金资助: 国家自然科学基金(81673508,82173738); 军队后勤科研项目(CLB19J049); 中央高校基本科研业务费专项(3192020009); 甘肃省青年科技基金计划(20JR10RA014); 联勤保障部队第九四〇医院院内应急医学科研项目(20yjky017)
通讯作者: 王荣     E-mail: wangrong-69@163.com
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引用本文:

王子晗,郭茜文,马江红,程俊飞,赵安鹏,李文斌,王荣. 红景天苷对急进高原大鼠肺组织的保护作用[J]. 浙江大学学报(医学版), 2022, 51(4): 422-429.

WANG Zihan,GUO Qianwen,MA Jianghong,CHENG Junfei,ZHAO Anpeng,LI Wenbin,WANG Rong. Protective effect of salidroside on lung tissue in rats exposed rapidly to high altitude. J Zhejiang Univ (Med Sci), 2022, 51(4): 422-429.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0157        https://www.zjujournals.com/med/CN/Y2022/V51/I4/422

组 别

SaO 2(%)

PaCO 2(mmHg)

PaO 2(mmHg)

血液酸碱度

血红蛋白(g/L)

SBC

实际碳酸氢盐(mmol/L)

空白对照组

95.90±1.86

40.53±6.60

83.27±12.65

7.42±0.05

125.83±8.42

26.83±5.36

26.73±6.37

模型对照组

86.05±3.54 *

39.05±7.07

63.20±11.24 *

7.22±0.24 *

137.50±3.02 *

18.55±8.39 *

18.72±9.20 *

红景天胶囊组

88.75±1.14 #*

37.03±4.27

58.63±1.77 *

7.35±0.01 #

122.50±8.60 #

21.10±1.78 *

20.67±2.53 *

红景天苷小剂量组

87.87±2.26 *

41.87±3.19

56.87±3.58 *

7.36±0.03 #

132.83±8.42

23.70±2.34

24.15±2.62

红景天苷中剂量组

89.08±1.73 #*

42.55±2.14

58.08±3.42 *

7.39±0.03 #

125.83±10.82 #

25.30±2.23 #

25.78±2.46 #

红景天苷大剂量组

89.83±2.40 #*

41.78±3.62

60.53±6.20 *

7.38±0.01 #

130.50±9.18

24.47±1.89 #

24.83±2.42 #

表1  各组血气分析指标检测结果比较

组 别

MCP-1(ng/mL)

IL-6(pg/mL)

γ干扰素(pg/mL)

IL-1β(pg/mL)

GSH(g/L)

T-SOD(U/mg蛋白)

MDA(nmol/mL)

空白对照组

10.34±3.28

30.19±10.67

70.69±23.64

8.65±3.05

9.04±1.23

3.66±0.35

1.08±0.08

模型对照组

35.38±2.28 *

142.54±43.89 *

21.87±12.23 *

22.70±7.40 *

5.62±0.21 *

2.37±0.57 *

1.32±0.10 *

红景天胶囊组

33.03±4.59

123.30±63.13 *

38.26±22.35

10.23±6.10 #

7.46±1.87 *#

2.95±0.51 *#

0.95±0.07 #

红景天苷小剂量组

19.27±3.24 #△

35.70±22.22 #△

27.11±9.87 *

7.23±2.93 #

7.44±0.57 *#

3.54±0.39 #△

1.15±0.18 #

红景天苷中剂量组

27.43±2.00

49.64±18.84 #△

58.76±28.84

13.56±5.65 #

8.94±1.45 #△

3.28±0.44 #

1.15±0.06 #

红景天苷大剂量组

17.88±3.66 #△

20.55±8.93 #△

34.07±25.64 *

8.51±4.84 #

10.14±0.92 #△

3.40±0.32 #

0.92±0.12 *#

表2  各组血清炎症因子含量和肺组织氧化应激相关指标检测结果比较
图1  各组肺组织苏木精-伊红染色结果 A:空白对照组肺泡腔内无分泌物,肺泡壁薄而完整(箭头所示);B:模型对照组肺泡腔内可见大量渗出物,细胞壁变厚,支气管腔变形(箭头所示);C:红景天胶囊组肺泡腔内分泌物减少,肺泡壁相对完整(箭头所示);D:红景天苷小剂量组肺泡腔内分泌物减少,细胞壁变薄(箭头所示);E:红景天苷中剂量组肺泡腔内分泌物减少,细胞壁变薄,肺泡壁较完整(箭头所示);F:红景天苷大剂量组肺泡腔仅少量分泌物,肺泡壁薄而完整(箭头所示). 标尺 =50 μm.
图2  各组肺组织中闭合蛋白电泳图
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