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中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2020, Vol. 15 ›› Issue (01) : 26 -36. doi: 10.3877/cma.j.issn.1673-9450.2020.01.005

所属专题： 文献；

论著

血必净对烧伤犬血管通透性和液体需求量的影响
张文华1, 唐富波1, 王海滨2, 李雨梦3, 胡泉4, 李琳5, 谭志军6, 胡森1, 白晓东6,†()   
  1. 1. 100853　北京，解放军总医院医学创新研究部创伤修复与组织再生研究中心
    2. 100048　北京，解放军总医院第四医学中心检验科
    3. 455000　安阳市中医院脑病科
    4. 100048　北京，解放军总医院第四医学中心烧伤整形科
    5. 100048　北京，解放军总医院第四医学中心麻醉科
    6. 518055　深圳大学总医院整形美容科
  • 收稿日期:2019-12-28 出版日期:2020-02-01
  • 通信作者: 白晓东
  • 基金资助:
    军委后勤保障部重大项目(ALP19J001); 国家自然科学基金(81471872)

Effect of Xuebijing on vascular permeability and fluid demand in burn dogs

Wenhua Zhang1, Fubo Tang1, Haibin Wang2, Yumeng Li3, Quan Hu4, Lin Li5, Zhijun Tan6, Sen Hu1, Xiaodong Bai6,†()   

  1. 1. Research Center of Trauma Repair and Tissue Regeneration, Medical Innovation Research Department, Chinese PLA General Hospital, Beijing 100853, China
    2. Department of Laboratory, Fourth Medical Center of PLA General Hospital, Beijing 100048, China
    3. Department of Encephatopathy, Anyang Traditional Chinese Medicine Hospital, Anyang 455000 , China
    4. Department of Burns and Plastic Surgery, Fourth Medical Center of PLA General Hospital, Beijing 100048, China
    5. Department of Anesthesiology, Fourth Medical Center of PLA General Hospital, Beijing 100048, China
    6. Department of Plastic and Aesthetic Surgery, Shenzhen University General Hospital, Shenzhen 518055, China
  • Received:2019-12-28 Published:2020-02-01
  • Corresponding author: Xiaodong Bai
  • About author:
    Corresponding author: Bai Xiaodong, Email:
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引用本文：

张文华, 唐富波, 王海滨, 李雨梦, 胡泉, 李琳, 谭志军, 胡森, 白晓东. 血必净对烧伤犬血管通透性和液体需求量的影响[J/OL]. 中华损伤与修复杂志(电子版), 2020, 15(01): 26-36.

Wenhua Zhang, Fubo Tang, Haibin Wang, Yumeng Li, Quan Hu, Lin Li, Zhijun Tan, Sen Hu, Xiaodong Bai. Effect of Xuebijing on vascular permeability and fluid demand in burn dogs[J/OL]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2020, 15(01): 26-36.

目的

探讨血必净对烧伤犬血管通透性和液体需求量的影响。

方法

将24只雄性比格犬按照随机数字表法分成3组：乳酸林格氏液复苏组(LR组)，乳酸林格氏液复苏＋血必净组(LR＋XBJ组)和对照组(OC组)，每组8只。所有犬麻醉后行颈主动脉和静脉置管并插入尿管。3组犬均静脉注射丙泊酚(2 mg/kg)进行全身麻醉，OC组犬仅进行颈动静脉置管，未致伤；LR组和LR＋XBJ组犬进行颈动静脉置管后，量取背部50%总体表面积，备皮后3%凝固汽油均匀涂抹并点燃，持续燃烧30 s，致50%总体表面积全层烧伤。伤后12 h，给予犬丁丙诺啡(10 μg/kg)止痛。LR组根据Parkland公式静脉输入乳酸林格氏液(1%总体表面积为4 mL/kg，前8 h输入1/2，后16 h输入另1/2)；LR＋XBJ组在输入乳酸林格氏液(输入量和时间同LR组)的基础上，在伤后即刻和伤后4 h分别给予血必净注射1次，每次2 mL/kg。OC组仅输入与LR组和LR＋XBJ组等量的乳酸林格氏液。检测伤后即刻，伤后1、2、4、6、8和24 h 7个时间点各组犬血流动力学指标[平均动脉压(MAP)、心输出量指数(CI)、血管外肺水指数(ELWI)和肺血管通透性指数(PVPI)]、血浆容量、红细胞压积、尿累积量与累计净输入量、各脏器组织(心脏、肺脏、肾脏、小肠)含水率、血管通透性、中性粒细胞浸润数量及髓过氧化物酶(MPO)和中性粒细胞弹性蛋白酶(NE)活性。数据比较采用单因素方差分析、t检验和χ2检验。

结果

伤后即刻，3组间MAP、CI、ELWI、PVPI比较差异均无统计学意义(P值均大于0.05)；伤后1、2、4、6、8和24 h，LR组和LR＋XBJ组的MAP、CI、ELWI、PVPI比OC组均明显降低，3组间比较差异均有统计学意义(P值均小于0.05)；伤后1、2、4、6、8和24 h，LR组的MAP和CI与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)；伤后1、2、4 h，LR组的ELWI和PVPI与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)，而伤后6、8、24 h LR组的ELWI和PVPI与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)。伤后即刻，3组间血浆容量和红细胞压积比较差异均无统计学意义(P值均大于0.05)；伤后1、2、4、6、8和24 h，LR组和LR＋XBJ组的血浆容量和红细胞压积比OC组均明显降低，3组间比较差异均有统计学意义(P值均小于0.05)；伤后1、2、6、8、24 h，LR组的血浆容量与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)，伤后4 h LR组的血浆容量与LR＋XBJ组比较，差异有统计学意义(P<0.05)；伤后1、6、8、24 h，LR组的红细胞压积与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)，伤后2、4 h LR组的红细胞压积与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)。伤后即刻，伤后1、2、4、6、8、24 h, LR组和LR＋XBJ组尿量比较差异均无统计学意义(P值大于0.05)；伤后即刻，伤后1、2 h，LR组的累积净输入量与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)，而伤后4、6、8、24 h LR组的累积净输入量与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)。伤后24 h，LR组和LR＋XBJ组的心脏、肺脏、肾脏、小肠中的含水率、血管通透性和中性粒细胞浸润数量比OC组均明显增加，3组间比较差异均有统计学意义(P值均小于0.05)；伤后24 h，LR组心脏、肾脏中的含水率和血管通透性与LR＋XBJ组比较，差异均无统计学意义(P值均大于0.05)，肺脏、小肠中的含水率和血管通透性与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)；伤后24 h，LR组肾脏组织中的中性粒细胞浸润数量与LR＋XBJ组比较，差异无统计学意义(P>0.05)，心脏、肺脏、小肠中的中性粒细胞浸润数量与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)。伤后24 h，LR组和LR＋XBJ组的心脏、肺脏、肾脏、小肠中的MPO和NE含量比OC组均明显增加，3组间比较差异均有统计学意义(P值均小于0.05)；伤后24 h，LR组心脏、肾脏组织中的MPO含量与LR＋XBJ组比较，差异均无统计学意义(P＝0.05、P>0.05)，肺脏、小肠中的MPO含量与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)；伤后24 h，LR组肾脏组织中的NE含量与LR＋XBJ组比较，差异无统计学意义(P>0.05)，心脏、肺脏、小肠中的NE含量与LR＋XBJ组比较，差异均有统计学意义(P值均小于0.05)。

结论

血必净注射液能抑制蛋白酶引起的血管通透性升高和组织水肿，明显降低烧伤犬复苏液体需求量。

关键词: 烧伤, 狗, 血流动力学, 血必净注射液, 脏器组织
Objective

To investigate the effect of Xuebijing on vascular permeability and fluid demand in burn dogs.

Methods

Twenty four male Beagle dogs were divided into 3 groups according to the random number table method: lactated ringer′s solution resuscitation group (LR group), lactated Ringer′s solution resuscitation+ Xuebijing group (LR+ XBJ group) and control group (OC group), 8 dogs in each group. All the dogs were anesthetized and then the carotid aorta and venous catheters were placed and urinary catheters were inserted. All the dogs in the 3 groups were injected intravenously with propofol (2 mg/kg) for general anesthesia. The dogs in the OC group received only jugular arteriovenous catheterization without injury. In the LR group and LR+ XBJ group, after jugular arteriovenous catheterization, 50% of the total body surface area of the back was measured. After skin preparation, 3% naphtha was evenly smeared and ignited, and continued to burn for 30 s, resulting in 50% of the total body surface area of the burn. Twelve hours after the injury, buprenorphine (10 μg/kg) was given to relieve pain. In the LR group, the lactated Ringer′s solution was intravenously injected according to the Parkland formula (1% of the total body surface area was 4 mL/kg, and the first 8 h was entered as 1/2, the second 16 h as the other entered); in the LR+ XBJ group, based on the lactated Ringer′s solution (the input amount and time were the same as those in the LR group), Xuebijing injection was given at a dose of 2 mL/kg immediately after the injury and 4 h after the injury. In the OC group, only the same amount of lactated Ringer′s solution as the LR group and the LR+ XBJ group was input. The hemodynamic indicators [mean arterial pressure (MAP), cardiac output index (CI), extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI)], plasma volume, hematocrit, urine accumulation and cumulative net input, moisture content of various organ tissues (heart, lung, kidney, small intestine), vascular permeability, neutrophil infiltration number, and myeloperoxidase (MPO) and neutrophil elastase(NE) at immediately after injury, 1, 2, 4, 6, 8, and 24 h after injury were detected. Data were compared with one-way analysis of variance, t test, and χ2 test.

Results

Immediately after injury, there were no statistically significant differences in MAP, CI, ELWI, and PVPI between the 3 groups (with P values above 0.05); 1, 2, 4, 6, 8, and 24 h after injury, the MAP, CI, ELWI, and PVPI in the LR group and LR+ XBJ group were significantly lower than those in the OC group, and the differences between the 3 groups were statistically significant (with P values below 0.05). At 1, 2, 4, 6, 8 and 24 h after injury, there were no statistically significant difference in MAP and CI between the LR group and the LR+ XBJ group (with P values above 0.05); there were no statistically significant differences in ELWI and PVPI between the LR group and the LR+ XBJ group at 1, 2 and 4 h after injury (with P values above 0.05), but at 6, 8, and 24 h after injury, the ELWI and PVPI of the two groups were statistically significant (with P values below 0.05). Immediately after injury, there were no statistically significant differences in plasma volume and hematocrit between the three groups (with P values above 0.05); at 1, 2, 4, 6, 8 and 24 h after injury, the plasma volume and hematocrit in the LR group and the LR+ XBJ group were significantly lower than those in the OC group, the differences of the 3 groups were statistically significant (with P values below 0.05); at 1, 2, 6, 8, and 24 h after injury, there were no statistically significant difference in plasma volume between the LR group and the LR+ XBJ group (with P values above 0.05); compared with the LR+ XBJ group, the plasma volume of the LR group at 4 h after injury was statistically significant (P<0.05); at 1, 6, 8, and 24 h after injury, the hematocrit of the two groups were no statistically significant (with P values above 0.05), and the hematocrit of the two groups at 2 and 4 h after injury were statistically significant (with P values below 0.05). Immediately after injury, 1, 2, 4, 6, 8, and 24 h after injury, there was no statistically significant difference in urine output between LR group and LR+ XBJ group (with P values above 0.05). Immediately after injury, 1, 2 h after injury, the cumulative net input in the LR group and LR+ XBJ group were no statistically significant(with P values above 0.05), but at 4, 6, 8 and 24 h after injury, the cumulative net input in the two groups were statistically significant (with P values below 0.05). At 24 h after injury, the water content, vascular permeability, and neutrophil infiltration in the heart, lung, kidney, and small intestine of the LR group and LR+ XBJ groups were significantly higher than those in the OC group, the differences of the three group was statistically significant (with P values below 0.05); at 24 h after injury, the water content and vascular permeability in the heart and kidney of the LR group were no statistically significantly different from those in the LR+ XBJ group (with P values above 0.05), and in the lung and small intestine were statistically significant (with P values below 0.05). At 24 h after injury, there was no significant difference in the number of neutrophil infiltration in the kidney tissue of the LR group and LR+ XBJ group (P>0.05), the number of neutrophil infiltration in the heart, lung, and small intestine in the 2 groups were statistically significant (with P values below 0.05). At 24 h after injury, the contents of MPO and NE in the heart, lung, kidney, and small intestine of the LR group and LR+ XBJ group were significantly higher than those in the OC group, the differences between the 3 groups were statistically significant (with P values below 0.05); 24 h after injury, the MPO content in heart and kidney tissues of LR group was not significantly difference from that of LR+ XBJ group (P=0.05, P>0.05); compared with the LR+ XBJ group, the MPO content in the lung and small intestine in the LR group were statistically significant (with P values below 0.05). At 24 h after injury, there was no statistically significant difference in NE content in kidney tissue between LR group and LR+ XBJ group (P>0.05). The differences of NE content in heart, lung, and small intestine of the two groups were statistical significance (with P values below 0.05).

Conclusion

Xuebijing injection can inhibit the increase of vascular permeability and tissue edema caused by protease, and significantly reduce the resuscitation fluid demand of burn dogs.

Key words: Burns, Dogs, Hemodynamics, Xuebijing injection, Organ tissue
表1 血必净对3组犬不同时间血流动力学指标的影响(±s)
组别 犬数(只) MAP(mmHg)
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 143.88±10.32 144.23±11.12 142.75±10.10 142.25±10.99 142.75±12.05 142.75±9.63 143.13±11.33
LR组 8 143.00±10.57 71.11±10.21 88.75±12.16 101.63±12.07 105.75±13.49 117.00±12.92 123.00±10.73
LR＋XBJ组 8 140.87±10.42 70.36±11.25 91.37±11.92 105.63±12.64 116.37±13.00 122.87±13.55 127.00±9.73
F值 ? 0.18 15.34 56.78 28.23 17.54 9.85 8.05
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.55 0.44 0.65 1.60 0.89 0.78
P值 ? ? >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
组别 犬数(只) CI (L/min－1/m－2)
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 5.23±0.33 5.23±0.37 5.35±0.41 5.27±0.29 5.36±0.46 5.21±0.32 5.32±0.46
LR组 8 5.25±0.46 1.25±0.43 1.96±0.49 2.22±0.56 2.53±0.41 3.16±0.57 3.46±0.33
LR＋XBJ组 8 5.36±0.45 1.38±0.49 1.89±0.43 2.44±0.52 2.75±0.56 3.04±0.63 3.53±0.48
F值 ? 0.02 2.78 3.52 13.55 19.94 10.76 17.30
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.37 0.40 0.65 1.90 0.35 1.05
P值 ? ? >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
组别 犬数(只) ELWI (mL/kg－1)
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 7.98±0.46 8.15±0.58 8.12±0.53 8.06±0.49 8.27±0.42 8.02±0.67 7.93±0.62
LR组 8 8.10±0.49 13.86±1.45 15.37±1.43 14.41±1.33 12.68±1.45 11.36±1.89 9.97±1.32
LR＋XBJ组 8 8.11±0.67 11.55±1.34 13.38±1.35 12.43±1.35 11.37±1.12 10.45±1.27 9.66±1.55
F值 ? 0.11 11.68 12.47 22.96 30.09 25.11 16.97
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.69 0.80 1.85 3.09 4.25 3.87
P值 ? ? >0.05 >0.05 >0.05 <0.05 <0.05 <0.05
组别 犬数(只) PVPI
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 2.65±0.29 2.57±0.33 2.72±0.24 2.80±0.27 2.68±0.28 2.48±0.31 2.75±0.27
LR组 8 2.76±0.43 3.82±0.27 4.85±0.28 4.32±0.30 4.13±0.28 3.87±0.24 3.46±0.31
LR＋XBJ组 8 2.82±0.42 3.51±0.25 4.22±0.23 3.98±0.24 3.86±0.27 3.55±0.37 3.18±0.28
F值 ? 0.02 14.56 15.21 64.55 37.46 36.20 25.72
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.49 0.80 1.85 .09 4.25 3.87
P值 ? ? >0.05 >0.05 >0.05 <0.05 <0.05 <0.05
表2 血必净对3组犬不同时间血浆容量和红细胞压积的影响(±s)
组别 犬数(只) 血浆容量(mL)
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 618.38±22.77 619.63±27.86 617.25±25.55 612.25±24.48 614.00±24.21 610.50±34.35 617.25±28.67
LR组 8 612.13±22.59 484.88±31.23 380.13±25.10 397.88±28.28 427.88±28.93 454.50±32.08 503.63±25.72
LR＋XBJ组 8 617.00±23.76 491.63±29.38 396.13±27.23 432.75±25.00 453.63±28.14 476.13±29.58 513.75±28.30
F值 ? 0.16 52.91 208.24 156.93 110.22 55.60 41.54
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.45 1.22 2.61 1.81 1.40 0.75
P值 ? ? >0.05 >0.05 <0.05 >0.05 >0.05 >0.05
组别 犬数(只) 红细胞压积(%)
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
OC组 8 40.20±0.94 40.28±0.88 40.23±1.05 40.53±1.06 39.91±0.93 39.96±0.96 40.46±0.70
LR组 8 40.34±0.83 48.05±1.53 52.50±1.62 51.03±1.71 48.24±1.69 45.71±1.69 44.70±1.72
LR＋XBJ组 8 40.73±0.88 47.86±1.30 49.13±1.57 48.30±1.40 47.34±1.67 44.96±1.84 43.98±1.47
F值 ? 0.76 98.40 155.77 118.27 77.17 32.80 22.01
P值 ? >0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
t值 ? ? 0.26 4.23 3.48 1.07 0.85 0.91
P值 ? ? >0.05 <0.05 <0.05 >0.05 >0.05 >0.05
表3 血必净对50%总体表面积烧伤犬不同时间尿累积量和累计净输入量的影响(mL/kg, ±s)
组别 犬数(只) 尿累积量
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
LR组 8 0 20.86±3.31 39.50±5.66 80.63±8.68 124.88±11.15 161.88±11.89 488.75±34.74
LR＋XBJ组 8 0 20.25±2.25 39.00±3.74 80.13±5.17 119.13±13.58 159.88±15.31 485.56±33.53
t值 ? ? 0.44 0.21 0.14 0.93 0.29 0.37
P值 ? ? >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
组别 犬数(只) 累积净输入量
伤后即刻 伤后1 h 伤后2 h 伤后4 h 伤后6 h 伤后8 h 伤后24 h
LR组 8 0 130.00±17.82 234.75±38.50 501.63±50.83 641.13±40.60 830.88±68.29 1 404.50±96.42
LR＋XBJ组 8 0 125.13±14.21 222.63±34.98 346.38±48.92 430.25±49.92 517.63±59.65 852.88±99.67
t值 ? ? 0.61 0.66 6.22 9.27 9.77 11.25
P值 ? ? >0.05 >0.05 <0.05 <0.05 <0.05 <0.05
表4 血必净对3组犬伤后24 h各脏器组织含水率、血管通透性及中性粒细胞浸润数量的影响(±s)
组别 犬数(只) 含水率(%)
心脏 肺脏 肾脏 小肠
OC组 8 72.51±2.85 71.66±2.43 72.20±1.90 69.58±2.31
LR组 8 79.36±3.63 81.31±2.87 82.78±2.54 78.47±1.94
LR＋XBJ组 8 79.77±1.94 77.24±2.70 81.02±2.68 72.59±1.65
F值 ? 15.90 26.25 44.83 41.51
P值 ? <0.05 <0.05 <0.05 <0.05
χ2值 ? 0.28 2.92 1.35 6.53
P值 ? >0.05 <0.05 >0.05 <0.05
组别 犬数(只) 血管通透性
心脏 肺脏 肾脏 小肠
OC组 8 0.17±0.05 0.13±0.04 0.24±0.05 0.19±0.05
LR组 8 0.37±0.07 0.33±0.05 0.44±0.07 0.41±0.06
LR＋XBJ组 8 0.33±0.05 0.24±0.05 0.39±0.06 0.31±0.06
F值 ? 25.12 37.26 23.70 31.80
P值 ? <0.05 <0.05 <0.05 <0.05
t值 ? 1.22 3.24 1.59 3.60
P值 ? >0.05 <0.05 >0.05 <0.05
组别 犬数(只) 中性粒细胞浸润量(个)
心脏 肺脏 肾脏 小肠
OC组 8 5.13±1.13 7.13±1.81 7.13±1.36 8.63±1.41
LR组 8 22.38±2.77 26.88±2.85 24.38±2.56 28.25±2.49
LR＋XBJ组 8 19.13±2.47 21.13±2.47 21.63±3.07 20.38±3.38
F值 ? 133.64 141.37 115.79 119.39
P值 ? <0.05 <0.05 <0.05 <0.05
t值 ? 2.47 4.31 1.95 5.31
P值 ? <0.05 <0.05 >0.05 <0.05
表5 血必净对3组犬伤后24 h各脏器组织MPO和NE活性的影响(±s)
组别 犬数(只) MPO(U/g)
心脏 肺脏 肾脏 小肠
OC组 8 0.41±0.08 0.71±0.13 0.52±0.15 0.57±0.15
LR组 8 1.90±0.17 2.31±0.24 1.85±0.21 2.20±0.24
LR＋XBJ组 8 1.71±0.18 1.33±0.16 1.65±0.20 1.60±0.21
F值 ? 228.01 157.10 112.19 131.20
P值 ? <0.05 <0.05 <0.05 <0.05
t值 ? 2.14 9.65 1.93 5.30
P值 ? 0.05 <0.05 >0.05 <0.05
组别 犬数(只) NE(pg/mL)
心脏 肺脏 肾脏 小肠
OC组 8 88.54±16.81 105.12±34.81 117.25±19.27 108.86±16.57
LR组 8 261.50±21.51 424.72±29.78 377.89±25.26 383.19±24.72
LR＋XBJ组 8 216.55±24.17 261.53±25.79 354.83±27.41 286.54±40.26
F值 ? 145.40 221.75 283.71 185.42
P值 ? <0.05 <0.05 <0.05 <0.05
t值 ? 3.93 11.72 1.75 5.79
P值 ? <0.05 <0.05 >0.05 <0.05
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