Effects Of Preoperative Vitamin-Rich Carbohydrate Loading On The Surgical Stress Response And Postoperative Cognitive Dysfunction In Elderly Rats

Objectives:With the acceleration of an aging population,postoperative cognitive dysfunction(POCD)has become a large problem.Preoperative carbohydrate(CHO)loading has been reported to attenuate surgery stress response and insulin resistance,and decrease postoperative complications.In this study,a vitamin-rich carbohydrate beverage was administered before surgery in an animal model to investigate its effects on the surgical stress response and S-100B levels.The present study also aimed to investigate whether preoperative vitamin-rich carbohydrate loading has an effect on POCD,endoplasmic reticulum(ER)stress,and apoptosis.Methods:1.The effects of preoperative vitamin-rich carbohydrate loading on the surgical stress response and S-100 β after splenectomy in elderly ratsThirty aged male Sprague-Dawley rats were randomly assigned to three groups:control group(n=6),fasting group(n=12),and carbohydrate-treated group(CHO group,n = 12)Rats in the control group were not given any treatment.Rats in the fasting group received splenectomy after 12 h of fasting.In the CHO group,rats were given 5 ml of vitamin-rich carbohydrate by gavage 2 h before surgery.Fasting plasma glucose,insulin,insulin resistance(HOMA-IR index,IRI),S-100β level,inflammatory mediators IL-1β,IL-6,TNF-α,and GLP-1 level were assessed after surgery(postoperative day(POD)1 and 3)2.Preoperative vitamin-rich carbohydrate loading alleviates postoperative cognitive dysfunction in aged ratsEighty male Sprague-Dawley rats(20-month old)were randomly assigned to four groups(20 per group):control group(no anesthesia and surgery),fasting group(fasting 14 h before surgery),water group(ingest water 3 h before surgery),and carbohydrate-treated group(CHO group,ingest vitamin-rich carbohydrate 3 h before surgery).The POCD rat model was established by splenectomy under intraperitoneal injection of pentobarbital sodium.Cognitive function was assessed using the Morris water maze(MWM)after surgery.Apoptosis in the hippocampal tissue was evaluated with TUNEL assays.Furthermore,the levels of endoplasmic reticulum(ER)stress markers and apoptosis related proteins(GRP78,eIF2a,Beclinl,Bax and Bcl-2)in the hippocampus were examined by Western blot analysis3.Effects of single-dose and double-dose vitamin-rich carbohydrate preoperative loading on ER stress and apoptosis in aged ratsTwenty-five aged male Sprague-Dawley rats were randomly assigned to five groups(5 per group):control group(no anesthesia and surgery),fasting group(fasting 14 h before surgery),water group(ingest water 3 h before surgery),single-dose carbohydrate-treated group(SCHO group,ingest 12 ml vitamin-rich carbohydrate 3 h before surgery),and double-dose carbohydrate-treated group(BCHO group,ingest 24 and 12 ml vitamin-rich carbohydrate on the evening before surgery and 3 h before surgery respectively).The levels of endoplasmic reticulum(ER)stress markers and apoptosis related proteins(GRP78,Beclinl,Bax and Bcl-2)in the hippocampus were examined by Western blot analysis on postoperative day 1.Results:1.Postoperative insulin resistance was significantly greater in the fasting group than in the control and CHO group.The median plasma S-100 β level was significantly higher in the fasting group than in the control and CHO groups on POD 1.The median plasma IL-1β level was significantly lower in the CHO group than in the fasting group on POD 1;however,no other differences in the concentrations of immunological biomarkers of stress were found between the fasting group and the CHO group2.The vitamin-riched carbohydrate-treated animals performed better in the MWM tests than animals in fasting and water groups.Furthermore,preoperative carbohydrate loading reduced ER stress and neuronal apoptosis in the hippocampus of aged rats,as indicated by TUNEL assays and protein biomarkers of GRP78,eIF2a,Beclinl,Bax and Bcl-23.Preoperative double-dose vitamin-rich carbohydrate loading can’t reduce ER stress and neuronal apoptosis in the hippocampus of aged rats undergoing splenectomy,as indicated by protein biomarkers of GRP78,Beclinl,Bax and Bcl-2Conclusions:1.Preoperative vitamin-rich carbohydrate loading attenuated the metabolic aspect of the surgical stress response,but the effect of vitamin-rich carbohydrate on inflammatory response in the aged rats after splenectomy is uncertain and needs further study2.Preoperative vitamin-rich carbohydrate loading reduced the level of S-100β in plasma of rats after operation,which indicated that it might reduce the brain damage caused by surgical stress.3.Preoperative vitamin-rich carbohydrate loading could improve POCD by attenuating ER stress and neural apoptosis,providing a basis as a potential treatment against POCD4.Preoperative double-dose vitamin-rich carbohydrate loading can’t reduce ER stress and neuronal apoptosis in the hippocampus of aged rats undergoing splenectomy.For preoperative carbohydrate loading,double dose is not better than single dose.