Characteristics Of Secondary Liver Injury After Intestinal Firearm Penetrating Injury In High Altitude Cold Environment And Treatment Research

Objective: The purpose of this study were(1)to establish a model of enterofirearm through injury in cold plateau environment,compare the difference of secondary liver injury after enterofirearm through injury at different time points and in plain environment,summarize the change characteristics and possible causes of secondary liver injury,and explore possible signal pathways.(2)To observe the therapeutic effect of curcumin nanocrystalline injection(CNI)on secondary liver injury,and explore the possible signaling pathways for improving apoptosis,oxidative stress and inflammation of hepatocytes.(3)To observe the effect of damage control surgery(DCS)combined with CNI in the treatment of model pigs with intestinal firearm through injury in cold environment at high altitude,so as to provide reference for trauma treatment.Methods:Part I: Healthy Landrace piglets of the same age were divided into plain normal temperature(NT)group and high altitude cold(HC)group by random number table method after adaptive feeding.Group NT was placed in an experimental chamber at an altitude of 800 m and(24±2)℃ in a simulated plain environment at normal temperature for 48 hours.The HC group was placed in an experimental chamber with an altitude of6000 m and(8±2)℃ in a simulated high altitude cold environment at normal temperature for 48 hours.Each group was treated according to the established procedure,followed by(a)clinical observation of general conditions and vital signs,(b)automatic blood cell analyzer for blood cells,(c)ELISA for inflammatory factors,markers of oxidative stress in liver tissue and inflammatory factors in serum,(d)blood gas analyzer for acid-base balance disorder,(e)automatic blood coagulation analyzer and TEG detector for clotting related indicators,(f)automatic biochemical analyzer for liver function,(g)H&E staining for liver histopathological injury,(h)TUNEL staining for liver apoptosis,(i)immunohistochemistry or signalling protein,(j)Western blot or signalling protein.Part II:The piglets were divided into 3 groups,NT group and HC group were the same as the first part,and group 3 was HCC group(CNI treatment model pigs).Each group was processed according to the established procedure,followed by(a)clinical observation of vital signs,(b)automatic blood cell analyzer for blood cells,(c)ELISA for inflammatory factors,markers of oxidative stress in liver tissue and inflammatory factors in serum,(d)blood gas analyzer for acid-base balance disorder,(e)automatic blood coagulation analyzer and TEG detector for clotting related indicators,(f)automatic biochemical analyzer for liver function,(g)H&E staining for liver histopathological injury,(h)TUNEL staining for liver apoptosis,(i)immunohistochemistry or signalling protein,(j)Western blot or signalling protein.Part III: Piglets of the same age were divided into 5 groups with 10 piglets per group: HC group,HCC group,HCT group,HCD group and HDC group.HC group and HCC group were the same as the first and second parts.The HCT group was the model pigs treated with traditional surgery.The HCD group was the model pigs treated with DCS.HDC group was the model pig treated with DCS and CNI.Each group was processed according to the established procedure,followed by(a)observation of abdominal injury,(b)clinical observation of vital signs,(c)automatic blood cell analyzer for blood cells,(d)automatic biochemical analyzer for liver function,(e)automatic hemagglutination analyzer and TEG detector for coagulation related indicators,(f)ELISA for serum inflammatory factors,(g)Observation of operation-related indicators,early postoperative complications and survival analysis.Results: Part I:(a)The dual stress of high altitude cold,low pressure,hypoxic environment,and intestinal firearm penetrating injury can induce more obvious secondary liver damage than the plain environment,accompanied by more obvious coagulation dysfunction,which may be related to more obvious endotoxemia,acid-base imbalance,inflammatory response,oxidative stress,and liver cell apoptosis.(b)Hepatocyte apoptosis may be related to activation of HMGB1/TRL4/NF-κB signaling pathway.Part II:(a)Early treatment with CNI for intestinal firearm penetrating injury in piglets in high-altitude cold environments can alleviate inflammation,endotoxemia,acid-base imbalance,oxidative stress,hepatocyte apoptosis,and subsequently alleviate secondary liver damage such as liver pathological damage,liver dysfunction,and coagulation dysfunction.(b)The mechanism of CNI improving secondary liver injury may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway improves apoptosis of liver,inhibits Keap1-Nrf2-ARE signaling pathway improves oxidative stress of liver,and inhibits NO/i NOS/NF-κB The signaling pathway improves inflammation related responses of liver.Part III:(a)DCS early treatment for intestinal firearm penetrating injury in piglets in high-altitude cold environments improves surgical related indicators and accelerates anesthesia recovery and postoperative recovery compared to traditional surgery;reduce the incidence of early postoperative complications in the short term;reduce blood inflammation,endotoxemia,coagulation dysfunction,and secondary liver injury.(b)DCS combined with CNI can maintain the stability of vital signs faster and correct the disorder of blood index better than DCS in the treatment of piglets with intestinal firearm penetrating injury in the high-altitude cold environments.Conclusions:(1)Compared with abdominal intestinal firearm penetrating injury in plain environments,abdominal intestinal firearm penetrating injury in high-altitude cold environments results in more obvious secondary liver injury in the body,accompanied by more obvious coagulation dysfunction,which may be related to more obvious endotoxemia,acid-base imbalance,inflammatory response,oxidative stress,and liver cell apoptosis.(2)Secondary liver injury after abdominal firearm penetrating injury in a high-altitude cold environment,characterized by impaired liver function,liver cell edema,necrosis,and apoptosis,may be related to the activation of the HMGB1/TLR4/NF-κB signaling pathway.(3)Early treatment of intestinal firearm penetrating injury in piglets under high-altitude cold environment with curcumin nanocrystalline injection can alleviate secondary liver injury,which may be related to inhibiting the HMGB1/TLR4/NF-κB signaling pathway to improve liver cell apoptosis,inhibiting the Keap1-Nrf2-ARE signaling pathway to improve liver oxidative stress,and inhibiting the NO/i NOS/NF-κB signaling pathway to improve liver inflammatory response.(4)DCS combined with CNI can better and faster maintain the stability of vital signs,accelerate anesthesia recovery and postoperative recovery,reduce the incidence of early postoperative complications,alleviate blood inflammation,acid-base imbalance,endotoxemia,coagulation and liver dysfunction,and improve survival time in piglets with intestinal firearm penetrating injury in high-altitude cold environments compared to traditional surgery,and maintains vital signs more quickly and corrects blood disorders better than DCS.