The Study Of Effect And Action Mechanism Of Graphene Far-infrared Heating Film Of Propofol Postoperative Fatigue

Postoperative Fatigue(POF)is a period of loss of energy,weakness,and fatigue of varying duration and degree during the recovery process after surgery.POF increases the risk of psychological disorders such as depression;prolongs the patient’s recovery time;reduces the patient’s quality of life;and increases the medical burden on society.Current research on the pathogenesis of POF is scarce,and there is a lack of effective clinical treatment.Studies have shown that hypothermia in the perioperative period prolongs the recovery time of patients and increases postoperative complications,and it is may be one of the important factors that induce POF.Far-infrared heat therapy is a non-invasive treatment modality with the advantages of safety,convenience and no side effects,which is widely used in clinical disease treatment and post-operative rehabilitation.Graphene,a new nanomaterial,is widely used in biomedical field,and the far-infrared light waves generated by single-layer graphene film have more efficient"resonance effect" with the body.Based on this,this study intends to investigate the role and mechanism of graphene far-infrared heat therapy in preventing perioperative hypothermia and improving postoperative fatigue by establishing anesthesia-induced hypothermia animal model and POF animal model.PurposesThe purpose of this study was to investigate the anti-fatigue effect and mechanism of graphene far-infrared heat therapy thermotherapy on a mouse model of 70%hepatectomy-induced POF.The animal model of anesthesia-induced hypothermia and the animal model of 70%hepatectomy-induced POF were used to evaluate the effect of graphene far-infrared heat therapy on the improvement of perioperative hypothermia and POF,and to investigate the mechanism of the effect of graphene far-infrared heat therapy on the improvement of POF by activating brown fat(BAT)thermogenesis around fat energy metabolism.Methods1.Study on the effect of graphene far-infrared heat therapy on improving POF(1)Effect of graphene far-infrared heat therapy on POF induced by 70%hepatectomy:male C57BL/6J mice were randomly divided into:normal control group(Con),POF model group(Mon),POF+graphene far-infrared heat therapy group(Mon+Gra),POF+carbon fiber far-infrared heat therapy group(Mon+Car).The Mon+Gra group was treated with graphene farinfrared heat therapy for 7 days before surgery,and the Mon+Car group was treated with carbon fiber far-infrared heat therapy for 7 days before surgery,and the body temperature capsule was buried in the abdominal cavity on the day of surgery.The general status of mice was observed after surgery,and the Open-Filed test(OFT)was performed on the 1st,3rd and 5th days after surgery,the Treadmill test(TT)was performed on the 2nd,4th and 6th days after surgery,the swimming exhaustion test and the grasping force test were performed on the 3rd day after surgery,and the behavioral experiments were all performed 30 min after the heat therapy.The mice were monitored for 24h postoperative core temperature,anal temperature and scapular body surface temperature after thermotherapy,and the mortality rate was counted within one week after surgery.(2)Effect of graphene far-infrared thermotherapy on sodium pentobarbital-induced hypothermia:Male C57BL/6J mice were selected and divided into:normal control group(Con),sodium pentobarbital anesthesia group(NEMB),sodium pentobarbital anesthesia+graphene far-infrared thermotherapy group(NEMB+Gra),sodium pentobarbital anesthesia+carbon fiber far-infrared thermotherapy group(NEMB+Car).group without anesthesia and heat treatment,NEMB,NEMB+Gra and NEMB+Car groups were administered with 2%sodium pentobarbital solution by 0.1mL/10g intraperitoneal injection,and the body temperature capsule was buried into the mice’s abdominal cavity before the experiment,and each group was administered at the same time on the day of the experiment,and the mice of NEMB group were put in room temperature after administration,and the mice of NEMB+Gra group were put in the graphene far-infrared heat generation film box In order to ensure that the mice did not crowd each other for heating,each mouse was placed in a single cage,and the ambient temperature was kept quiet during the experiment.The mice’s core body temperature data were recorded throughout the process.2.The mechanism of graphene far-infrared heat therapy to improve POFThe experimental animals were grouped and treated in the same way as above.After surgery,OFT and TT experiments were performed to verify the success of the model and the effectiveness of graphene far-infrared heat therapy on improving POF in mice.On the third day after surgery,blood was removed by execution,and the following steps were performed:blood was removed from the scapular brown fat(iBAT),white fat from the abdominal sulcus(WAT),liver(all but the left lateral lobe and middle lobe),and serum for glucose(GLU),serum lactic acid(LAC),and serum lactate(Glucose).Lactic acid(LAC),non-esterified fatty acids(NEFA),triglycerides(TG)and other biochemical parameters,and adipose tissue for protein blotting(Western blot,WB)and hematoxylin-eosin(TG).The biochemical parameters such as trtlyceride(TG),western blot(WB)and hematoxylineosin(HE)staining of adipose tissues were examined,and AMP-activated protein kinase(PGC-1α),AMP-activated protein kinase(PGC-1α),PGC-1αand PGC-1α were examined.AMP-activated protein kinase(AMPK),Phosphorylation AMP-activated protein kinase(P-AMPK),Phosphorylation mammalian target of rapamycin(P-AMPK),Phosphorylation AMPactivated protein kinase(P-AMPK),and Phosphorylation AMP-activated protein kinase(P-AMPK).mammalian target of rapamycin(P-mTOR),mitochondrial brown lipolytic coupling protein 1(UCP1),interleukin-6(IL6),liver for hepatic glycogen detection experiments,iBAT,abdominal sulcus WAT and liver as far as possible were weighed after complete stripping.Results1.Study on the effect of graphene far-infrared thermal therapy to improve POF(1)Effect of graphene far-infrared heat therapy on POF induced by 70%hepatectomy:①General status:compared with the Con group,mice in the Mon group,Mon+GRA group and Mon+Car group showed a decrease in body weight;compared with the Con group,mice in the Mon group showed squinting and hair boring,and the squinting and hair scores in the Mon+GRA group were significantly lower than those in the Mon group;②OFT experiment:compared with the Con group,the total spontaneous activity distance moved by mice in the Mon group was significantly reduced on days 1 and 3;compared with the Mon group,the Mon+Gra group significantly increased the total spontaneous activity distance moved by POF mice on days 1 and 3 after surgery;③TT experiment:compared with the Con group,the distance moved by mice in the Mon group was significantly reduced on days 2 and 4 after surgery;compared with the Mon group mice’s grasping force;④Swimming exhaustion experiment:Compared with the Con group,the exhaustion swimming time of the mice in the Mon group significantly decreased;Compared with the Mon group,the Mon+Gra group significantly increased the exhaustion swimming time of the mice;⑤Grip force experiment:Compared with the Con group,the force grip force of the mice in the Mon group significantly decreased;Compared with the Mon group,the Mon+Gra group significantly increased the mice’s grasping force;⑥Body temperature monitoring experiment:70%of mice in hepatectomy showed perioperative hypothermia,and graphene far-infrared heat therapy prevented the occurrence of perioperative hypothermia;both graphene farinfrared heat therapy and carbon fiber far-infrared heat therapy increased the body surface temperature and anal temperature of scapula of mice,and the core body temperature,body surface temperature and anal temperature of mice in Mon+Gra group were significantly higher compared with Mon+Car group;⑦Graphene far-infrared heat therapy reduced the mortality of mice within one week after surgery.(2)Effect of graphene far-infrared heat therapy on sodium pentobarbital-induced hypothermia:sodium pentobarbital anesthesia caused a significant decrease in the core body temperature of mice,which reached the lowest value at 30 min after anesthesia,followed by a slow increase.graphene far-infrared heat therapy and carbon fiber far-infrared heat therapy significantly increased the core body temperature of mice at 35 min,40 min and 45 min time points after anesthesia relative to the Mon+The core body temperature of mice in the Mon+Gra group increased significantly at 35 min,40 min and 45 min after anesthesia compared with the Mon+Car group;graphene far-infrared heat therapy could shorten the awakening time of mice.2.Study on the mechanism of graphene far-infrared heat therapy to improve POF①The effect of graphene far-infrared heat therapy on brown adipocyte morphology:iBAT body weight ratio decreased in Mon group compared with Con group.Compared with the Mon group,the iBAT to body weight ratio increased significantly in the Mon+Gra group.Due to the forced depletion of iBAT,the cytoplasmic composition of cells in the Mon group increased and HE staining became darker.The area and lipid droplet diameter were significantly decreased in the Mon group compared to the Con group.The lipid droplet diameter and area were significantly increased in the Mon+Gra group compared with the Mon group;②Effects of graphene farinfrared heat therapy on WAT cell morphology:The Mon+Gra group was significantly higher and more vascular than the Mon group.③Effects of graphene far-infrared heat therapy on serum GLU and liver glycogen in POF mice:The serum GLU and liver glycogen levels were significantly decreased in the Mon group compared with the Con group.Compared with the Mon group,the serum GLU and liver glycogen levels in the Mon+Gra group were significantly increased;④The effects of graphene far-infrared heat therapy on serum TG and NEFA levels in POF mice:TG and NEFA levels were significantly lower in the Mon group compared with the Con group;TG and FFA levels were significantly higher in the Mon+Gra group compared with the Mon group;⑤POF mice:compared with the Con group,serum LAC levels were significantly lower in the Mon group;compared with the Mon group,serum LAC levels were significantly higher in the Mon+Gra group;⑥Graphene far-infrared thermotherapy increased UCP1 expression and promoted iBAT non-shivering thermogenesis through activating the PAMPK/PGC-1α pathway:compared with the Con group,70%liver resection significantly reduced the expression level of P-AMPK and the level of the important thermogenic factor PGC-1α.The expression levels of P-AMPK and PGC-1α protein were significantly higher in the Mon+Gra group compared with the Mon group,and the expression levels of UCP1 were not significantly improved in the Mon group compared with the Con mice,and the expression levels of UCP1 were significantly higher in the Mon+Gra group compared with the Mon group;⑦Graphene far-infrared heat therapy inhibited IL-6 expression levels in iBAT:IL-6 expression levels were significantly increased in the Mon group compared with the Con group;IL6 expression levels were significantly decreased in the Mon+Gra group compared with the Mon group;⑧Graphene far-infrared heat therapy increased P-mTOR expression levels in iBAT:P-mTOR expression levels were significantly decreased in the Mon group compared with the Con group;P-mTOR expression levels were significantly increased in the Mon+Gra group compared with the Mon group.ConclusionWe first found that graphene far-infrared heat therapy could effectively improve POF symptoms in mice,and also that it could effectively prevent postoperative hypothermia during real-time body temperature monitoring,and not only through simple heat transfer.Further study demonstrated that graphene far infrared could upregulate UCP1 protein expression by activating the P-AMPK/PGC-1α pathway,which in turn activates brown fat thermogenesis and plays an important role in suppressing the high expression of IL-6 caused by 70%hepatectomy.The effect of graphene far-infrared heat therapy on improving postoperative fatigue and maintaining homeostasis of glucolipid metabolism in mice was verified by biochemical indexes such as blood glucose,liver glycogen,triglycerides and free fatty acids.