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1.陆军军医大学(第三军医大学)第二附属医院营养科,重庆
2.陆军军医大学(第三军医大学)军事预防医学系营养与食品安全研究中心,重庆市医学营养研究中心,营养与健康重庆市重点实验室,重庆
糜漫天,E-mail: mantian_mi@tmmu.edu.cn
王建,E-mail: wangjian_xq@tmmu.edu.cn
收稿日期:2024-12-16,
修回日期:2025-02-17,
纸质出版日期:2025-03-30
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辛文彬,白倩,倪向敏,等.一种复方营养制剂对大鼠急性创伤后伤口愈合的影响研究[J].陆军军医大学学报,2025,47(06):506-518.DOI:10.16016/j.2097-0927.202412081.
XIN W B,BAI Q,NI X M,et al.Effect of a compound nutrition preparation on wound healing after acute trauma in rats[J].J Army Med Univ,2025,47(06):506-518.DOI:10.16016/j.2097-0927.202412081.
辛文彬,白倩,倪向敏,等.一种复方营养制剂对大鼠急性创伤后伤口愈合的影响研究[J].陆军军医大学学报,2025,47(06):506-518.DOI:10.16016/j.2097-0927.202412081. DOI:
XIN W B,BAI Q,NI X M,et al.Effect of a compound nutrition preparation on wound healing after acute trauma in rats[J].J Army Med Univ,2025,47(06):506-518.DOI:10.16016/j.2097-0927.202412081. DOI:
目的
2
一种复方营养制剂对急性创伤后伤口愈合的作用效果及其原理的初步探讨。
方法
2
60只雄性SD大鼠通过外科手术方法成功构建皮肤创面模型后,采用随机数字表法将大鼠分为对照组(CON组)、乳清蛋白组(whey protein,WP组)、低剂量复方营养制剂组(low-dose nutritional formula,LDF组)和高剂量复方营养制剂组(high-dose nutritional formula,HDF组),每组15只。各组大鼠于术后次日起给予对应营养干预2周,干预期间观察记录各组大鼠的伤口情况并测量伤口面积。分别于术后第3、7、14天取材,采用试剂盒检测血清白蛋白(albumin, ALB)、前白蛋白(prealbumin, PA)、总蛋白(total protein, TP)、炎症因子(TNF-α、IL-1β、IL-6、IL-10)、免疫球蛋白(IgA、IgG、IgM)及羟脯氨酸(hydroxyproline, Hyp)水平;HE染色观察伤口创面组织病理形态学变化;Masson染色观察伤口创面组织胶原纤维沉积情况;免疫组化染色评估伤口创面组织血管生成情况。
结果
2
与CON组比较,WP组、LDF组、HDF组的创面愈合速度、胶原合成及血管生成速度明显加快(
P
<
0.05),其中HDF组效果最明显。术后第3天,与CON组相比,WP组、LDF组和HDF组血清ALB、PA、TP水平显著升高(
P
<
0.05),TNF-α、IL-1β水平显著降低(
P
<
0.05),而IL-10水平显著升高(WP组除外),LDF组、HDF组血清IgG、IgM水平显著升高(
P
<
0.05),HDF组血清IgA水平显著升高(
P
<
0.05);术后第7天,与CON组相比,HDF组ALB、PA和TP水平显著升高(
P
<
0.05),TNF-α、IL-1β、IL-6水平显著降低(
P
<
0.05),而IL-10水平显著升高(
P
<
0.05),LDF组、HDF组血清IgG、IgM水平显著升高(
P
<
0.05),HDF组血清IgA水平显著升高(
P
<
0.05);术后第14天,与CON组相比,HDF组ALB、TP水平显著升高(
P
<
0.05),IL-1β水平显著降低(
P
<
0.05),IgG、IgM水平显著升高(
P
<
0.05)。
结论
2
本研究中的复方营养制剂能够促进急性伤口愈合,其可能原因与制剂能改善大鼠营养状况,促进胶原蛋白合成,减轻机体炎症反应并增强免疫功能有关。
Objective To explore the efficacy of a compound nutrition preparation on wound healing after acute trauma and investigate the underlying mechanism primarily. Methods After skin wound model was successfully constructed on totally 60 male SD rats surgically
they were randomly divided into control group (CON group)
whey protein group (WP group) and low- and high-dose nutritional formula groups (LDF and HDF groups)
with 15 animals in per group. From the next day after surgery
the rats in each group were given co
rresponding nutritional interventions for 2 weeks. During the intervention
the wound conditions were observed and recorded
and the wound area was measured. The samples were collected on the 3rd
7th and 14th days after surgery
respectively. Serum albumin (ALB)
prealbumin (PA)
total protein (TP)
inflammatory factors (TNF-α
IL-1β
IL-6 and IL-10)
immunoglobulins (IgA
IgG and IgM) and hydroxyproline (Hyp) were detected by the corresponding reagent kits. The histopathologic changes of wound were observed with HE staining. Masson staining was used to observe the collagen fiber deposition in wound tissue. The angiogenesis of wound tissue was evaluated by immunohistochemical staining. Results Compared with the CON group
the wound healing speed
collagen synthesis and angiogenesis speed were significantly accelerated in the WP group
LDF group and HDF group (
P
<
0.05)
and the effects were the most obvious in the HDF group. On the 3rd day after surgery
in the WP
LDF and HDF groups
the serum ALB
PA and TP levels were significantly increased (
P
<
0.05)
serum TNF-α and IL-1β levels were obviously decreased (
P
<
0.05)
and serum IL-10 level was notably increased (except WP group) when compared with the CON group. The serum IgG and IgM levels were significantly increased in the LDF group and HDF group (
P
<
0.05) and significant increment of IgA was only observed in the HDF group (
P
<
0.05). On the 7th day after modeling
the levels of ALB
PA and TP were significantly increased (
P
<
0.05)
the levels of TNF-α
IL-1β and IL-6 were obviously decreased (
P
<
0.05)
and the levels of IL-10 were remarkably increased (
P
<
0.05) in the HDF group than the CON group; The LDF group and HDF group had significantly elevated serum IgG and IgM levels (
P
<
0.05)
but only the former group had statistically increased serum IgA level (
P
<
0.05). On t
he 14th day after modeling
the HDF group had significantly increased levels of ALB and TP (
P
<
0.05)
decreased levels of IL-1β (
P
<
0.05)
and raised levels of IgG and IgM when compared with the CON group (
P
<
0.05). Conclusion Our compound nutrition preparation promotes wound healing in rat model of acute trauma
which might be related to its improving the nutritional status
promoting collagen synthesis
and thus alleviating inflammatory response and enhancing immune function.
LAI J Q , CHEN X R , LIN S , et al . Progress in research on the role of clinical nutrition in treating traumatic brain injury affecting the neurovascular unit [J]. Nutr Rev , 2023 , 81 ( 8 ): 1051 - 1062 . DOI: 10.1093/nutrit/nuac099 http://dx.doi.org/10.1093/nutrit/nuac099 .
TRIBBLE D R , MURRAY C K , LLOYD B A , et al . After the battlefield: infectious complications among wounded warriors in the trauma infectious disease outcomes study [J]. Mil Med , 2019 , 184 ( Suppl 2 ): 18 - 25 . DOI: 10.1093/milmed/usz027 http://dx.doi.org/10.1093/milmed/usz027 .
刘良明 . 战创伤休克早期救治研究进展与思考 [J]. 陆军军医大学学报 , 2022 , 44 ( 20 ): 2025 - 2029 . DOI: 10.16016/j.2097-0927.202205151 http://dx.doi.org/10.16016/j.2097-0927.202205151 .
LIU L M . Advances and thinking for early treatment of war wound and traumatic shock [J]. J Army Med Univ , 2022 , 44 ( 20 ): 2025 - 2029 . DOI: 10.16016/j.2097-0927.202205151 http://dx.doi.org/10.16016/j.2097-0927.202205151 .
CLARK R K , STAMPAS A , KERR K W , et al . Evaluating the impact of using a wound-specific oral nutritional supplement to support wound healing in a rehabilitation setting [J]. Int Wound J , 2023 , 20 ( 1 ): 145 - 154 . DOI: 10.1111/iwj.13849 http://dx.doi.org/10.1111/iwj.13849 .
LIU T F , LU Y F , ZHAN R X , et al . Nanomaterials and nanomaterials-based drug delivery to promote cutaneous wound healing [J]. Adv Drug Deliv Rev , 2023 , 193 : 114670 . DOI : 10.1016/j. addr.2022.114670 http://dx.doi.org/10.1016/j.addr.2022.114670 .
GRADA A , PHILLIPS T J . Nutrition and cutaneous wound healing [J]. Clin Dermatol , 2022 , 40 ( 2 ): 103 - 113 . DOI: 10.1016/j. clindermatol.2021.10.002 http://dx.doi.org/10.1016/j.clindermatol.2021.10.002 .
CZORLICH P , DREIMANN M , EMAMI P , et al . Body mass index >35 as independent predictor of mortality in severe traumatic brain injury [J]. World Neurosurg , 2017 , 107 : 515 - 521 . DOI: 10.1016/j.wneu.2017.08.010 http://dx.doi.org/10.1016/j.wneu.2017.08.010 .
MELO P G , MOTA J F , DE BARROS NUNES C A , et al . Effects of oral nutritional supplementation on patients with venous ulcers: a clinical trial [J]. J Clin Med , 2022 , 11 ( 19 ): 5683 . DOI: 10.3390/jcm11195683 http://dx.doi.org/10.3390/jcm11195683 .
MUNOZ N , POSTHAUER M E , CEREDA E , et al . The role of nutrition for pressure injury prevention and healing: the 2019 international clinical practice guideline recommendations [J]. Adv Skin Wound Care , 2020 , 33 ( 3 ): 123 - 136 . DOI: 10.1097/01. ASW .0000653144.90739. ad http://dx.doi.org/10.1097/01.ASW.0000653144.90739.ad .
MACKAY D , MILLER A L . Nutritional support for wound healing [J]. Altern Med Rev , 2003 , 8 ( 4 ): 359 - 377 .
糜漫天 , 蔡东联 . 军事营养医学 [M]. 北京 : 人民军医出版社 , 2015 .
MI M T , CAI D L . Military Nutritional Medicine . Beijing : People’s Military Medical Press , 2015 .
GREGORI P , FRANCESCHETTI E , BASCIANI S , et al . Immunonutrition in orthopedic and traumatic patients [J]. Nutrients , 2023 , 15 ( 3 ): 537 . DOI: 10.3390/nu15030537 http://dx.doi.org/10.3390/nu15030537 .
BLASS S C , GOOST H , TOLBA R H , et al . Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronu-trients and glutamine: a PRCT [J]. Clin Nutr , 2012 , 31 ( 4 ): 469 - 475 . DOI: 10.1016/j. clnu.2012.01.002 http://dx.doi.org/10.1016/j.clnu.2012.01.002 .
CEREDA E , KLERSY C , SERIOLI M , et al . A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial [J]. Ann Intern Med , 2015 , 162 ( 3 ): 167 - 174 . DOI: 10.7326/M14-0696 http://dx.doi.org/10.7326/M14-0696 .
CORSETTI G , ROMANO C , PASINI E , et al . Diet enrichment with a specific essential free amino acid mixture improves healing of undressed wounds in aged rats [J]. Exp Gerontol , 2017 , 96 : 138 - 145 . DOI: 10.1016/j. exger. 2017.06.020 http://dx.doi.org/10.1016/j.exger.2017.06.020 .
YANG T , YAN X H , CAO Y B , et al . Meta-analysis of glutamine on immune function and post-operative complications of patients with colorectal cancer [J]. Front Nutr , 2021 , 8 : 765809 . DOI: 10.3389/fnut.2021.765809 http://dx.doi.org/10.3389/fnut.2021.765809 .
BARCHITTA M , MAUGERI A , FAVARA G , et al . Nutrition and wound healing: an overview focusing on the beneficial effects of curcumin [J]. Int J Mol Sci , 2019 , 20 ( 5 ): 1119 . DOI: 10.3390/ijms20051119 http://dx.doi.org/10.3390/ijms20051119 .
DAHER G S , CHOI K Y , WELLS J W , et al . A systematic review of oral nutritional supplement and wound healing [J]. Ann Otol Rhinol Laryngol , 2022 , 131 ( 12 ): 1358 - 1368 . DOI: 10.1177/00034894211069437 http://dx.doi.org/10.1177/00034894211069437 .
BLASS S C , GOOST H , TOLBA R H , et al . Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: a PRCT [J]. Clin Nutr , 2012 , 31 ( 4 ): 469 - 475 . DOI: 10.1016/j. clnu.2012.01.002 http://dx.doi.org/10.1016/j.clnu.2012.01.002 .
ANGKA L , TANESE DE SOUZA C , BAXTER K E , et al . Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery [J]. Mol Ther , 2022 , 30 ( 10 ): 3270 - 3283 . DOI: 10.1016/j. ymthe. 2022.05.024 http://dx.doi.org/10.1016/j.ymthe.2022.05.024 .
MALONE-POVOLNY M J , MALONEY S E , SCHOENFI-SCH M H . Nitric oxide therapy for diabetic wound healing [J]. Adv Healthc Mater , 2019 , 8 ( 12 ): e1801210 . DOI: 10.1002/adhm.201801210 http://dx.doi.org/10.1002/adhm.201801210 .
BAE H J , LEE G Y , SEONG J M , et al . Outcomes with perioperative fat emulsions containing omega-3 fatty acid: a meta-analysis of randomized controlled trials [J]. Am J Health Syst Pharm , 2017 , 74 ( 12 ): 904 - 918 . DOI: 10.2146/ajhp151015 http://dx.doi.org/10.2146/ajhp151015 .
BERGER M M , BAINES M , RAFFOUL W , et al . Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations [J]. Am J Clin Nutr , 2007 , 85 ( 5 ): 1293 - 1300 . DOI: 10.1093/ajcn/85.5.1293 http://dx.doi.org/10.1093/ajcn/85.5.1293 .
LIN P H , SERMERSHEIM M , LI H C , et al . Zinc in wound healing modulation [J]. Nutrients , 2017 , 10 ( 1 ): 16 . DOI: 10.3390/nu10010016 http://dx.doi.org/10.3390/nu10010016 .
CHOW O , BARBUL A . Immunonutrition: role in wound healing and tissue regeneration [J]. Adv Wound Care , 2014 , 3 ( 1 ): 46 - 53 . DOI: 10.1089/wound.2012.0415 http://dx.doi.org/10.1089/wound.2012.0415 .
POLCZ M E , BARBUL A . The role of vitamin A in wound healing [J]. Nutr Clin Pract , 2019 , 34 ( 5 ): 695 - 700 . DOI: 10.1002/ncp.10376 http://dx.doi.org/10.1002/ncp.10376 .
BLASER A R , STARKOPF J , ALHAZZANI W , et al . Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines [J]. Intensive Care Med , 2017 , 43 ( 3 ): 380 - 398 . DOI: 10.1007/s00134-016-4665-0 http://dx.doi.org/10.1007/s00134-016-4665-0 .
CEREDA E , KLERSY C , SERIOLI M , et al . A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial [J]. Ann Intern Med , 2015 , 162 ( 3 ): 167 - 174 . DOI: 10.7326/M14-0696 http://dx.doi.org/10.7326/M14-0696 .
杨桦 , 陈国庆 . 免疫营养素在营养支持治疗中的作用 [J]. 中华消化外科杂志 , 2019 , 18 ( 10 ): 912 - 915 . DOI: 10.3760/cma.j.issn.1673-9752.2019.10.004 http://dx.doi.org/10.3760/cma.j.issn.1673-9752.2019.10.004 .
YANG H , CHEN G Q . Role of immune nutrients in the nutritional support treatment [J]. Chin J Dig Surg , 2019 , 18 ( 10 ): 912 - 915 . DOI: 10.3760/cma.j.issn.1673-9752.2019.10.004 http://dx.doi.org/10.3760/cma.j.issn.1673-9752.2019.10.004 .
KJAER M , FREDERIKSEN A K S , NISSEN N I , et al . Multinutrient supplementation increases collagen synthesis during early wound repair in a randomized controlled trial in patients with inguinal hernia [J]. J Nutr , 2020 , 150 ( 4 ): 792 - 799 . DOI: 10.1093/jn/nxz324 http://dx.doi.org/10.1093/jn/nxz324 .
DAIDONE C , SALIM N , SMITH L , et al . The role of fish skin xenografts in healing complex wounds: a brief case report [J]. Cureus , 2024 , 16 ( 3 ): e56156 . DOI: 10.7759/cureus.56156 http://dx.doi.org/10.7759/cureus.56156 .
HOBSON R . Vitamin E and wound healing: an evidence-based review [J]. Int Wound J , 2016 , 13 ( 3 ): 331 - 335 . DOI: 10.1111/iwj.12295 http://dx.doi.org/10.1111/iwj.12295 .
KANDHWAL M , BEHL T , SINGH S , et al . Role of matrix metalloproteinase in wound healing [J]. Am J Transl Res , 2022 , 14 ( 7 ): 4391 - 4405 .
ZINDER R , COOLEY R , VLAD L G , et al . Vitamin A and wound healing [J]. Nutr Clin Pract , 2019 , 34 ( 6 ): 839 - 849 . DOI: 10.1002/ncp.10420 http://dx.doi.org/10.1002/ncp.10420 .
WANG X , YU Z P , ZHOU S N , et al . The effect of a compound protein on wound healing and nutritional status [J]. Evid Based Complement Alternat Med , 2022 , 2022 : 4231516 . DOI: 10.1155/2022/4231516 http://dx.doi.org/10.1155/2022/4231516 .
LAI J Q , CHEN X R , LIN S , et al . Progress in research on the role of clinical nutrition in treating traumatic brain injury affecting the neurovascular unit [J]. Nutr Rev , 2023 , 81 ( 8 ): 1051 - 1062 . DOI: 10.1093/nutrit/nuac099 http://dx.doi.org/10.1093/nutrit/nuac099 .
ZHANG J , LI W H , YING Z W , et al . Soybean protein-derived peptide nutriment increases negative nitrogen balance in burn injury-induced inflammatory stress response in aged rats through the modulation of white blood cells and immune factors [J]. Food Nutr Res , 2020 , 64 : 64 . DOI: 10.29219/fnr. v64.3677 http://dx.doi.org/10.29219/fnr.v64.3677 .
LEITE C D S , BONAFÉ G A , PIRES O C , et al . Dipotassium glycyrrhizininate improves skin wound healing by modulating inflammatory process [J]. Int J Mol Sci , 2023 , 24 ( 4 ): 3839 . DOI: 10.3390/ijms24043839 http://dx.doi.org/10.3390/ijms24043839 .
DAI J Z , SHEN J J , CHAI Y M , et al . IL-1 β impaired diabetic wound healing by regulating MMP-2 and MMP-9 through the p38 pathway [J]. Mediators Inflamm , 2021 , 2021 : 6645766 . DOI: 10.1155/2021/6645766 http://dx.doi.org/10.1155/2021/6645766 .
WANG Y , WANG L , WEN Z , et al . High IL-6 and VEGF-A levels correlate with delayed wound healing in cervical lymph node tuberculosis patients [J]. Int J Tuberc Lung Dis , 2018 , 22 ( 10 ): 1227 - 1232 . DOI: 10.5588/ijtld.18.0027 http://dx.doi.org/10.5588/ijtld.18.0027 .
ASHCROFT G S , JEONG M J , ASHWORTH J J , et al . Tumor necrosis factor-alpha (TNF-α) is a therapeutic target for impaired cutaneous wound healing [J]. Wound Repair Regen , 2012 , 20 ( 1 ): 38 - 49 . DOI: 10.1111/j.1524-475X.2011.00748. x http://dx.doi.org/10.1111/j.1524-475X.2011.00748.x .
陈肖 , 阮一 , 何瑶 , 等 . 精氨酸强化的肠内营养对创伤患者预后及免疫功能影响的Meta分析 [J]. 中国药房 , 2019 , 30 ( 10 ): 1418 - 1423 . DOI: 10.6039/j.issn.1001-0408.2019.10.25 http://dx.doi.org/10.6039/j.issn.1001-0408.2019.10.25 .
CHEN X , RUAN Y , HE Y , et al . Effects of arginine-supplemented enteral nutrition on the prognosis and immune function of trauma patients: a meta-analysis [J]. China Pharm , 2019 , 30 ( 10 ): 1418 - 1423 . DOI: 10.6039/j.issn.1001-0408.2019.10.25 http://dx.doi.org/10.6039/j.issn.1001-0408.2019.10.25 .
BORTOLOTTI P , FAURE E , KIPNIS E . Inflammasomes in tissue damages and immune disorders after trauma [J]. Front Immunol , 2018 , 9 : 1900 . DOI: 10.3389/fimmu.2018.01900 http://dx.doi.org/10.3389/fimmu.2018.01900 .
YANG G N , STRUDWICK X L , BONDER C , et al . Effect of flightless I expression on epidermal stem cell niche during wound repair [J]. Adv Wound Care , 2020 , 9 ( 4 ): 161 - 173 . DOI: 10.1089/wound.2018.0884 http://dx.doi.org/10.1089/wound.2018.0884 .
XU J C , LIN Y , WANG Y , et al . Multifunctional regeneration silicon-loaded chitosan hydrogels for MRSA-infected diabetic wound healing [J]. Adv Healthc Mater , 2024 , 13 ( 10 ): e2303501 . DOI: 10.1002/adhm.202303501 http://dx.doi.org/10.1002/adhm.202303501 .
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