烧伤创疡再生医疗技术治疗眼镜蛇咬伤疗效观察

王世军 林欣欣 陈福伟 杨 旭

眼镜蛇是我国常见的剧毒蛇之一，主要分布于云南、贵州、浙江、福建等地区。流行病学资料显示，福建省是眼镜蛇咬伤的高发地区，每年因眼镜蛇咬伤入院的患者近百名，主要表现为水疱、灰黑斑及局部坏死等。目前，临床上多采用中草药外敷、植皮等方法予以治疗，但疗效不甚满意，极易导致咬伤部位进行性坏死而最终导致截肢。为提高眼镜蛇咬伤的治疗效果，笔者将临床常用于慢性难愈合创面治疗的烧伤创疡再生医疗技术应用于眼镜蛇咬伤患者的创面治疗，并与重组牛碱性成纤维细胞生长因子凝胶 （贝复新）治疗者进行了对比，疗效显著，现报告如下。

1 临床资料

1.1 一般资料

选取2010年6月至2016年6月福建中医药大学附属人民医院收治的120例眼镜蛇咬伤后局部皮肤出现灰黑斑的患者作为研究对象，并按照随机数表法将其随机分为治疗组 （60例）与对照组 （60例），其中治疗组男性41例、女性19例，年龄12～75岁 ［（51.05±12.32）岁］，咬伤至就诊时间为 2～120 h［（14.60±20.51） h］，咬伤位于上肢者28例、下肢者32例，入院前出现溃疡者8例、入院后出现溃疡者52例，轻度肿胀 （肿胀未越过1个大关节）者8例、中度肿胀 （肿胀越过1个大关节但未越过2个大关节）者17例、重度肿胀（肿胀越过2个大关节）者35例，Ⅰ度溃疡（溃疡面积＜4.0 cm ×4.0 cm［1］） 者53例、 Ⅱ度溃疡 （溃疡面积≥4.0 cm×4.0 cm且＜8.0 cm×8.0 cm［1］）者7例；对照组男性38例、女性22例，年龄10～74岁 ［（49.08±13.31）岁］，咬伤至就诊时间为1.8～115 h［（12.76±19.25）h］，咬伤位于上肢者26例、下肢者34例，入院前出现溃疡者5例、入院后出现溃疡者55例，轻度肿胀者11例、中度肿胀者20例、重度肿胀者29例，Ⅰ度溃疡者51例、Ⅱ度溃疡者9例。两组患者性别、年龄等一般资料对比，P均＞0.05，差异无统计学意义，具有可比性 （表1）。本研究经福建中医药大学附属人民医院伦理委员会批准，且所有患者均签署了知情同意书。

Cobra is one of the common venomous snakes in China，mainly in such provinces as Yunnan， Guizhou， Zhejiang and Fujian.Epide⁃miological data show that Fujian Province is a high⁃risk area of cobra bites.In Fujian，nearly 100 people are admitted into hospitals each year due to cobra bites.The main symptoms of cobra bites are blis⁃ters， gray black skin spots and local necrosis.At present， the external dressing with Chinese herbal medicine and skin grafting are commonly used to treat such injury in clinical practice，but the clinical efficacy is not satisfying because these approaches probably lead to progressive necrosis of the affected sites，resulting in amputation eventually.In order to improve the therapeutic effect of cobra bites，the author tentatively applied MEBT／MEBO ⁃a commonly used therapy in the treatment of chronic and hard⁃to⁃healing wounds ⁃in the treatment of cobra bites，compared its clinical efficacy with that of the recombined bovine basic fibroblast growth factor （bFGF） gel， and the results showed that the former had much better clinical efficacy than the later.

1.Clinical data

1.1 .General data

One hundred and twenty patients with gray black spots on their skin caused by cobra bites， admitted to The Affiliated People’s Hos⁃pital of Fujian University of Traditional Chinese Medicine from June 2010 to June 2016， were selected as the study subjects and were di⁃vided， according to the random number table， into a treatment group（60 cases） and a control group （60 cases）.In the treatment group：41 males and 19 females，aged 12-75 years old ［ （51.05±12.32）years］，time from being bitten to admission 2-120 h ［ （14.60 ±20.51） h］， 28 cases of upper limb bites， 32 cases of lower limb bites， 8 cases with ulcers before admission， 52 cases with ulcers after admission， 8 cases of mild swelling （smaller than 1 large joint）， 17 cases of moderate swelling（larger than 1 large joint but smaller than 2） ， 35 cases of severe swelling （larger than 2 large joints）， 53 ca⁃ses of degreeⅠ ulcer（ulcer area ＜4.0 cm ×4.0 cm［1］）， 7 cases of degreeⅡulcer（ulcer area≥4.0 cm×4.0 cm and ＜8.0 cm×8.0 cm）.In the control group：38 males and 22 females， aged 10-74 years old［ （49.08±13.31） years］， time from being bitten to admission 1.8-115 h［ （12.76±19.25） h］，26 cases of upper limb bites， 34 cases of lower limb bites， 5 cases with ulcers before admission， 55 cases with ulcers after admission， 11 cases of mild swelling，20 cases of moderate swelling，29 cases of severe swelling，51 cases of degreeⅠulcer，9 cases of degreeⅡulcer.The general data including gender，age and etc.were compared between the two groups and the results showed no statistically significant difference（all P ＞0.05）， presenting the comparability between the two groups（Table 1）.The study was approved by the Ethics Committee of The Affiliated People’s Hospital of Fujian University of Traditional Chi⁃nese Medicine and all patients signed the informed consent.

表1 两组患者一般资料对比Table 1 Comparison of general data between the two groups

1.2 纳入标准

（1）明确眼镜蛇咬伤史且符合眼镜蛇咬伤临床表现者；（2）符合 《中国毒蛇学》中毒蛇咬伤所致皮肤溃疡的诊断标准［2］者；（3）咬伤部位位于四肢者；（4）溃疡程度为Ⅰ～Ⅱ度者；（5）年龄在10～75岁之间者；（6）对本研究知情，并自愿签署知情同意书者。

1.3 排除标准

（1）对本研究所用药物过敏者；（2）入院前1周内使用过溃疡相关外用药物者；（3）妊娠期妇女；（4）患有恶性肿瘤或严重心脑血管、肝、肾等系统原发性疾病者；（5）溃疡程度为Ⅲ度 （溃疡面积≥8.0 cm ×8.0 cm［1］） 或已深达骨骼并引发骨髓炎者。

1.2 .Inclusion criteria

Those who （1） have a history of cobra bite and the clinical mani⁃festations of cobra bites； （2） meet the diagnostic criteria for skin ulcers caused by poisonous snake bites in China Poisonous Snake Research［2］；（3） have the snake bites at four limbs； （4） suffer from degreeⅠ -Ⅱulcer； （5） aged between 10 and 75 years old； （6） are well informed of this study and voluntarily sign the informed consent.

1.3 .Exclusion criteria

Those who （1） are allergic to the drug used in this study； （2）have used ulcer⁃related topical drugs within 1 week before admission；（3） women in pregnancy； （4） have malignant tumors or severe primary diseases of cardiovascular system，cerebrovascular system，liver，kidney and etc.； （5） suffer from degreeⅢ ulcer（ulcer area≥8.0 cm ×8.0 cm［1］） or ulcers extending to bone and resulting in osteomyelitis.

2 方法

2.1 治疗方法

治疗组：在给予患者肌肉注射破伤风抗毒素、静脉滴注抗眼镜蛇毒血清+地塞米松+5%葡萄糖注射液、口服蛇伤胶囊和三草汤 （福建中医药大学附属人民医院内部制剂）以及加减蛇伤十三味方等全身综合治疗的同时，局部依次予以灰黑斑切开减压、清除坏死组织、生理盐水冲洗、消毒干纱布拭净后均匀涂抹湿润烧伤膏 （汕头市美宝制药有限公司生产，国药准字Z20000004），厚约0.5 cm（有潜腔者予以湿润烧伤膏药纱填塞），并覆盖无菌敷料固定包扎，每天换药1～2次，直至创面完全愈合。

对照组：在给予患者全身综合治疗的同时 （治疗方法同治疗组），局部依次予以灰黑斑切开减压、清除坏死组织、生理盐水冲洗、消毒干纱布拭净后均匀涂抹贝复新 （珠海亿胜生物制药有限公司生产，国药准字S20040001），30 IU／cm2（有潜腔者予以贝复新纱条填塞），并覆盖无菌敷料固定包扎，每天换药1～2次，直至创面完全愈合。

2.2 观察指标及疗效判定标准

分别于治疗30、60 d时参照国家中医药管理局发布的 《中医病证诊断疗效标准》［3］中蛇咬伤的疗效判定标准判定两组患者的治疗效果：治愈，创面完全愈合，患肢功能恢复；显效，肉芽组织生长良好，愈合创面面积＞70%，局部症状明显改善；有效，肉芽组织生长较好，愈合创面面积＞30%且≤70%，局部症状有所改善；无效，愈合创面面积≤30%，甚至扩大，局部症状无改善或加重；总有效率= （痊愈例数+显效例数+有效例数） ／总例数×100%。

2.3 统计学处理

采用SPSS 22.0统计软件对所得数据进行统计学分析，其中计量资料以 （x ± s） 表示，采用t检验或t＇检验；计数资料以频数或百分比表示，采用卡方检验或秩和检验；均以P＜0.05为差异具有统计学意义。

2.Methods

2.1 .Management methods

Treatment group： in addition to systemic comprehensive treatments，such as intramuscular injection of tetanus antitoxin，intravenous drip of Naja Antivenin+dexamethasone+5%glucose injection， oral adminis⁃tration of snake bite capsule and Sancao decoction （pharmaceutical prep⁃aration of The Affiliated People’s Hospital of Fujian University of Tradi⁃tional Chinese Medicine） and thirteen⁃ingredient Chinese herbs， the fol⁃lowing procedures were given to manage the local wounds including inci⁃sion and decompression of gray black spots， removal of necrotic tissues，normal saline rinsing， wiping with sterile dry gauze in turn before the ap⁃plication of MEBO（manufactured by Shantou MEBO Pharmaceutical Co.， Ltd.with China approval No.Z20000004）， about 0.5 cm in thick⁃ness （in case of hidden cavity， MEBO⁃impregnated gauze was filled in）， and the local wound was then covered and fixed with sterilized dressing.Dressing change was performed 1-2 times per day until the wound was healed completely.

Control group： in addition to systemic comprehensive treatments，such as intramuscular injection of tetanus antitoxin（same as that in the treatment group）， the local wound was given incision and decompression of gray black spots， removal of necrotic tissues， normal saline rinsing，wiping with sterile dry gauze in turn，followed by the application of bFGF （manufactured by Essex Bio⁃Technology Limited （Zhuhai） with China approval No.S20040001）， 30 IU／cm2（hidden cavity， if any，was filled with bFGF⁃impregnated gauze）， and the local wound was then covered and fixed with sterilized dressing.Dressing change was also per⁃formed 1-2 times per day until the wound was healed completely.

2.2 .Observational indexes and assessment criteria of clinical efficacy

After 30 and 60 days of treatment，the clinical efficacy of the two groups was assessed by reference to the clinical efficacy assessment standards for snake bites in Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditiona1 Chinese Medicine［3］issued by State Administration of Traditional Chinese Medicine.Cured：complete wound healing and good recovery of the injured limb； markedly effec⁃tive： granulation tissues grow well， the healed area is ＞70%and local symptoms get improvement substantially； effective： granulation tissues grow well，the healed area ＞30%and≤70%，and local symptoms get improvement；ineffective：the healed area≤30%， or the wound area has no change or even becomes larger，no improvement can be seen in local symptoms or symptoms are aggravated.Total effective rate=（number of healed cases+number of markedly effective cases+num⁃ber of effective cases） ／total number of cases×100%.

2.3 .Statistical analysis

The software SPSS 22.0 was adopted to analyze the study data，in which t test or t＇test was used to manage the measurement data expressed with（x± s） while Chi⁃square test or rank sum test was used to manage the count data expressed with frequency or percentage.P＜0.05 was considered as statistically significant difference.

3 结果

3.1 两组患者临床疗效对比

治疗30 d时，治疗组患者中治愈13例、显效21例、有效8例、无效18例、总有效率为70.00%；对照组患者中治愈8例、显效15例、有效8例、无效29例、总有效率为51.67%，两组对比，P＜0.05，差异具有统计学意义。治疗60 d时，治疗组患者中治愈53例、显效3例、有效2例、无效2例、总有效率为96.67%；对照组患者中治愈41例、显效4例、有效7例、无效8例、总有效率为86.67%，两组对比，P＜0.05，差异具有统计学意义 （表2）。

3.Results

3.1 .Comparison of clinical efficacy between the two groups

After 30 days of treatment，the total effective rate was 70.00%，with 13 cases cured， 21 cases markedly effective， 8 cases effective， and 18 cases ineffective in the treatment group， while in the control group，the total effective rate was 51.67%，with 8 cases cured，15 cases markedly effective， 8 cases effective and 29 cases ineffective， between which the comparison showed statistically significant difference（P＜0.05）.After 60 days of treatment， the total effective rate was 96.67%，with 53 patients cured， 3 cases markedly effective， 2 cases effective and 2 cases ineffective in the treatment group， which showed statistically sig⁃nificant difference as compared with the total effective rate 86.67%，41 cases cured， 4 cases markedly effective， 7 cases effective and 8 cases ineffective in the control group （P ＜0.05） （Table 2）.

表2 两组患者临床疗效对比 （例，%）Table 2 Comparison of clinical efficacy between the two groups（n，%）

3.2 两组患者创面愈合时间对比

治疗过程中，两组患者均未发生创面感染、过敏等不良反应，最终创面均完全愈合，其中治疗组患者的创面愈合时间为14～120 d［（43.63±20.48） d］，对照组患者的创面愈合时间为18～161 d ［ （66.93±36.45） d］，两组对比方差不齐采用t＇检验，t＇=-4.317，P=0.000，P＜0.05，差异具有统计学意义。

4 讨论

中医学认为，眼镜蛇蛇毒为风火毒，患者被咬伤后因火毒炽盛，热盛肉腐，腐肉化脓，导致局部组织溃烂、坏死［4］。火毒内袭入血分，热盛则迫血妄行，血行脉外，离经之血聚而成瘀，瘀血郁而化热，进而加重组织损伤。现代医学研究显示，眼镜蛇蛇毒中含有的透明质酸酶、蛋白水解酶、肌肉毒素、细胞毒素及磷脂酶A2等可导致细胞消融，局部组织缺血、缺氧及微循环障碍，血管壁通透性增加等，从而引发局部组织水肿及坏死［5］。

3.2 .Comparison of wound healing time between the two groups

During the treatment course，no adverse reactions such as wound infection and allergic reaction once occurred in the two groups and all the wounds of the two groups were completely healed at the end.The wound healing time was 14-120 （43.63±20.48） d in the treatment group while 18-161 （66.93±36.45） d in the control group，between which t＇test was used for the comparison given the unequal variance， and the results showed statistically significant difference （t＇=-4.317， P=0.000， P ＜0.05）.

4.Discussion

Traditional Chinese medicine holds that cobra venom is wind⁃fire toxin.After the patient is bitten by cobra，the fire toxin in the body leads to heat exuberance，as a result of which the injured muscle will rot and fester， eventually resulting in local tissue ulceration and necrosis［4］； The fire toxin will invade the blood， causing frenetic movement of blood，blood overflowing from the veins and arteries，and forming congestion.The stagnated blood in turn produces more heat，further aggravating the tissue damage.Modern medical research shows that hyaluronidase， pro⁃teolytic enzymes， myotoxin， cytotoxins and phospholipase A2contained in cobra venom can cause cell ablation，ischemia and hypoxia of local tissues， microcirculation disorders， increased permeability of vascular wall and etc.， further leading to local tissue edema and necrosis［5］.

Studies have shown that MEBO ⁃the core drug of MEBT／MEBO，has the effects of clearing heat，promoting blood circulation to improve blood stasis， and enhancing tissue regeneration［6-7］.Some active ingre⁃dients contained in MEBO can activate the potential regenerative cells in the wound tissues and transform them into stem cells which then prolifer⁃ate and differentiate in situ into tissue cells of all layers in the wound to regenerate and restore the wounded skin［8-9］.MEBO contains multiple nutrients such as polysaccharides， fatty acids， amino acids， vitamins，electrolytes and microelements，providing material guarantee for the regenerative restoration of wound tissues［10-12］.Therefore， the author applied MEBO in the treatment of cobra bite in this study and compared its clinical efficacy with that of bFGF.The results showed that after 30 days of treatment，the total effective rate was 70.00%in the treatment group and 51.67%in the control group，between which the comparison showed statistically significant difference（P ＜0.05）.After 60 days of treatment，the total effective rate was 96.67%in the treatment group and 86.67%in the control group，between which the comparison also showed statistically significant difference （P ＜ 0.05）.Finally， the wounds of patients in both groups were all completely healed.The wound healing time was（43.63±20.48） d in the treatment group and（66.93±36.45） d in the control group， between which the comparison showed statistically significant difference （P ＜0.05）.Thus， MEBT／MEBO can effectively promote the wound healing of patients with cobra bites， short⁃en the wound healing time and improve wound healing effect，of which the reason probably is that bFGF can only promote capillary regenera⁃tion， improve local blood circulation and accelerate wound healing，while， in contrast， besides the above same effects， MEBO can also clear heat and promote blood circulation to remove blood stasis，presenting better clinical efficacy than bFGF.

In summary， MEBT／MEBO in the treatment of cobra bite wounds can realize remarkable curative effects including shortening wound heal⁃ing time and improving wound healing effect，showing much high clinical application value.

研究显示，烧伤创疡再生医疗技术的核心药物湿润烧伤膏具有清热解毒、活血化瘀、生肌收敛之效［6-7］，其内含有的有效成分可激活创面组织中的潜能再生细胞，并将其转化为干细胞，再在原位增殖、分化为创面各层组织细胞，再生修复创面［8-9］；其含有的多糖、脂肪酸、氨基酸、维生素、电解质、微量元素等营养物质，可为创面的再生修复提供物质保障［10-12］。鉴于此，笔者于本研究中将其应用于眼镜蛇咬伤患者的创面治疗，并与贝复新治疗者进行了对比。结果显示，治疗30 d时，治疗组患者的总有效率为70.00%，对照组患者的总有效率为51.67%，两组对比，P＜0.05，差异具有统计学意义；治疗60 d时，治疗组患者的总有效率为96.67%，对照组患者的总有效率为86.67%，两组对比，P＜0.05，差异具有统计学意义；最终两组患者创面均完全愈合，其中治疗组患者的创面愈合时间为 （43.63±20.48）d，对照组患者的创面愈合时间为（66.93±36.45） d， 两组对比， P＜0.05，差异具有统计学意义。可见烧伤创疡再生医疗技术可有效促进眼镜蛇咬伤患者的创面愈合，缩短创面愈合时间，提高创面愈合效果。其原因可能为，贝复新仅具有促进毛细血管再生，改善局部血液循环，加速创面愈合等作用，而湿润烧伤膏还兼具中医学中清热解毒、活血化瘀等功效，故疗效明显优于贝复新。

综上所述，烧伤创疡再生医疗技术治疗眼镜蛇咬伤创面，可缩短创面愈合时间，提高创面愈合效果，疗效显著，临床应用价值较高。

（收稿日期：2018⁃12⁃14）