Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys

doi:10.12300/j.issn.1674-5817.2022.128

Abstract

Abstract:

Objective By observing the impact of Bevacizumab injection on the speed of wound healing and the expression of CD34 in cynomolgus monkeys, to verify its delayed wound healing mechanism, and to provide clinical reference for the dosage and frequency of Bevacizumab treatment for oncology surgery patients. Methods Six male cynomolgus monkeys underwent full-thickness skin resection on the back to establish a wound healing evaluation model. Three cynomolgus monkeys were randomly selected as the saline group, and the other three cynomolgus monkeys were allocated to the Bevacizumab treatment group. The monkeys of Bevacizumab group were administrated with Bevacizumab injection (30 mg/kg, i.v.) on day 0, day 4, day 8, and day 11, respectively. The monkeys of saline group were injected with the same volume of saline as the group receiving Bevacizumab. The blood routine test was conducted, and the wound healing of each group of cynomolgus monkeys was observed 28 days after operation. The wound healing rate was analyzed by software Image J, and the severity of the wound was assessed by scoring method. Wound healing skin samples of 6 cynomolgus monkeys were obtained after 4 weeks, and the expression level of CD34 in the wound skin tissues was detected using immunohistochemistry. Results A skin excision wound model has already been established in cynomolgus monkeys. The number of white blood cells and neutrophils in the blood of cynomolgus monkeys increased significantly on the 3^rd day after operation (P<0.05), and the number of white blood cells gradually returned to normal on the 7^th day, while the number of red blood cells, hemoglobin and hematocrit did not change significantly, suggesting that the animals were in good nutritional status. The Bevacizumab injection group wound healing rate was significantly slower than that of the saline group on day 7, and day 28^{(P<0.01, P<0.001). Microvessel density in the wound skin of Bevacizumab group appeared to be significantly lower than that of the saline group (P<0.01). Conclusion The injection of Bevacizumab may delay the wound healing by inhibiting the angiogenesis in the new skin tissue of the cynomolgus monkey. In clinical practice, the timing of giving a tumor patient a bevacizumab injection after surgery should be based on the pros and cons, and the duration, dosage, and frequency of the intervention should be chosen in a rational way.}

Key words: Bevacizumab injection, Wound healing, Wound score, CD34, Cynomolgus monkey

CLC Number:

Q95-33

Ping YANG, Li CUI, Cheng YU, Zhiyue WEN. Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys[J]. Laboratory Animal and Comparative Medicine, 2023, 43(1): 21-29.

Figures/Tables 5

References 30

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项目 Item	得分Score	描述 Description
伤口周围的皮肤颜色（距离伤口2 cm） Skin color around the wound (2 cm from the wound)	0	正常颜色或粉红色
	1	淡红色或有压之褪色的发红
	2	白色或灰白色
	3	深红色或压之不褪色的发红
	4	黑色或色素沉着过度
伤口周围组织水肿 Edema in wound surrounding tissue	0	无水肿或肿胀
	1	伤口周围非凹陷水肿范围<2 cm
	2	伤口周围非凹陷水肿范围≥2 cm
	3	伤口周围凹陷水肿范围<2 cm
	4	伤口周围凹陷水肿范围≥2 cm
渗出液类型 Type of exudate	0	无渗出液
	1	红色
	2	粉红色
	3	薄而透明，水性
	4	黄色或绿色，气味难闻
渗出量 Exudate amount	0	无渗出液
	1	伤口组织微湿，但无法测量
	2	伤口组织湿润，浸泡<25%的敷料
	3	伤口组织湿润，浸泡敷料的25%～75%
	4	伤口组织湿润，浸泡>75%的敷料

项目 Item	得分Score	描述 Description
伤口周围的皮肤颜色（距离伤口2 cm） Skin color around the wound (2 cm from the wound)	0	正常颜色或粉红色
	1	淡红色或有压之褪色的发红
	2	白色或灰白色
	3	深红色或压之不褪色的发红
	4	黑色或色素沉着过度
伤口周围组织水肿 Edema in wound surrounding tissue	0	无水肿或肿胀
	1	伤口周围非凹陷水肿范围<2 cm
	2	伤口周围非凹陷水肿范围≥2 cm
	3	伤口周围凹陷水肿范围<2 cm
	4	伤口周围凹陷水肿范围≥2 cm
渗出液类型 Type of exudate	0	无渗出液
	1	红色
	2	粉红色
	3	薄而透明，水性
	4	黄色或绿色，气味难闻
渗出量 Exudate amount	0	无渗出液
	1	伤口组织微湿，但无法测量
	2	伤口组织湿润，浸泡<25%的敷料
	3	伤口组织湿润，浸泡敷料的25%～75%
	4	伤口组织湿润，浸泡>75%的敷料

指标及组别 Index and group	手术后时间 Time after surgery/d
指标及组别 Index and group	0	3	7	14	28
WBC/(10⁹·L^-1)
生理盐水组 Saline group	13.20±0.08	31.00±1.05^△	14.65±0.10	15.64±0.08	18.70±0.69
贝伐珠单抗组 Bevacizumab group	12.15±0.09	25.25±0.08^△	13.48±0.04	15.72±0.50	17.14±0.23
RBC/(10¹²·L^-1)
生理盐水组 Saline group	5.80±0.21	6.01±0.48	6.22±0.13	5.88±0.35	5.99±0.34
贝伐珠单抗组Bevacizumab group	6.10±0.16	5.84±0.43	5.97±0.15	5.72±0.11	5.84±0.18
NEU/%
生理盐水组 Saline group	44.03±2.23	81.80±3.98^△	50.97±4.83	61.57±6.75	60.73±17.91
贝伐珠单抗组 Bevacizumab group	59.67±4.58	66.50±10.38	61.6±4.85	58.57±7.83	74.40±4.97
NEU/(10⁹·L^-1)
生理盐水组 Saline group	5.81±0.30	25.41±1.93^△△	7.46±0.66	9.61±1.01	11.53±3.54
贝伐珠单抗组 Bevacizumab group	7.26±0.59	16.80±2.62^△	8.31±0.66	9.25±1.39	12.74±0.83
LYM/%
生理盐水组 Saline group	50.37±2.92	14.53±3.75	43.17±3.76	30.97±6.64	30.37±14.77
贝伐珠单抗组 Bevacizumab group	33.30±4.35	28.43±9.75^*△	33.93±5.04	34.53±7.23	20.30±4.66
LYM/(10⁹·L^-1)
生理盐水组 Saline group	6.65±0.38	4.44±1.08	6.33±0.59	4.86±1.06	5.52±2.52
贝伐珠单抗组 Bevacizumab group	4.05±0.52	7.18±2.48	4.58±0.68	5.40±1.05	3.48±0.78
HG1B ρ/(g·L^-1)
生理盐水组 Saline group	140.00±3.06	147.00±7.00	149.33±5.84	144.33±7.17	139.00±3.61
贝伐珠单抗组 Bevacizumab group	150.00±5.57	142.33±7.06	142.67±7.84	140.67±2.73	140.33±3.84
HCT/%
生理盐水组 Saline group	45.93±1.13	47.27±2.20	47.93±2.15	45.73±2.22	44.97±1.90
贝伐珠单抗组 Bevacizumab group	48.70±1.65	45.40±2.39	45.93±2.05	45.87±1.22	45.30±1.56
EOS/%
生理盐水组 Saline group	0.87±0.29	0.43±0.34	1.23±0.29	2.13±0.95	3.50±3.06
贝伐珠单抗组Bevacizumab group	0.83±0.38	0.47±0.20	0.27±0.03	1.57±0.75	0.73±0.35
EOS/(10⁹·L^-1)
生理盐水组 Saline group	0.12±0.04	0.14±0.10	0.18±0.04	0.33±0.15	0.62±0.54
贝伐珠单抗组 Bevacizumab group	0.10±0.05	0.11±0.05	0.03±0.01	0.24±0.11	0.13±0.06

指标及组别 Index and group	手术后时间 Time after surgery/d
指标及组别 Index and group	0	3	7	14	28
WBC/(10⁹·L^-1)
生理盐水组 Saline group	13.20±0.08	31.00±1.05^△	14.65±0.10	15.64±0.08	18.70±0.69
贝伐珠单抗组 Bevacizumab group	12.15±0.09	25.25±0.08^△	13.48±0.04	15.72±0.50	17.14±0.23
RBC/(10¹²·L^-1)
生理盐水组 Saline group	5.80±0.21	6.01±0.48	6.22±0.13	5.88±0.35	5.99±0.34
贝伐珠单抗组Bevacizumab group	6.10±0.16	5.84±0.43	5.97±0.15	5.72±0.11	5.84±0.18
NEU/%
生理盐水组 Saline group	44.03±2.23	81.80±3.98^△	50.97±4.83	61.57±6.75	60.73±17.91
贝伐珠单抗组 Bevacizumab group	59.67±4.58	66.50±10.38	61.6±4.85	58.57±7.83	74.40±4.97
NEU/(10⁹·L^-1)
生理盐水组 Saline group	5.81±0.30	25.41±1.93^△△	7.46±0.66	9.61±1.01	11.53±3.54
贝伐珠单抗组 Bevacizumab group	7.26±0.59	16.80±2.62^△	8.31±0.66	9.25±1.39	12.74±0.83
LYM/%
生理盐水组 Saline group	50.37±2.92	14.53±3.75	43.17±3.76	30.97±6.64	30.37±14.77
贝伐珠单抗组 Bevacizumab group	33.30±4.35	28.43±9.75^*△	33.93±5.04	34.53±7.23	20.30±4.66
LYM/(10⁹·L^-1)
生理盐水组 Saline group	6.65±0.38	4.44±1.08	6.33±0.59	4.86±1.06	5.52±2.52
贝伐珠单抗组 Bevacizumab group	4.05±0.52	7.18±2.48	4.58±0.68	5.40±1.05	3.48±0.78
HG1B ρ/(g·L^-1)
生理盐水组 Saline group	140.00±3.06	147.00±7.00	149.33±5.84	144.33±7.17	139.00±3.61
贝伐珠单抗组 Bevacizumab group	150.00±5.57	142.33±7.06	142.67±7.84	140.67±2.73	140.33±3.84
HCT/%
生理盐水组 Saline group	45.93±1.13	47.27±2.20	47.93±2.15	45.73±2.22	44.97±1.90
贝伐珠单抗组 Bevacizumab group	48.70±1.65	45.40±2.39	45.93±2.05	45.87±1.22	45.30±1.56
EOS/%
生理盐水组 Saline group	0.87±0.29	0.43±0.34	1.23±0.29	2.13±0.95	3.50±3.06
贝伐珠单抗组Bevacizumab group	0.83±0.38	0.47±0.20	0.27±0.03	1.57±0.75	0.73±0.35
EOS/(10⁹·L^-1)
生理盐水组 Saline group	0.12±0.04	0.14±0.10	0.18±0.04	0.33±0.15	0.62±0.54
贝伐珠单抗组 Bevacizumab group	0.10±0.05	0.11±0.05	0.03±0.01	0.24±0.11	0.13±0.06

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