Protective Effect Of The Early Enteral Nutrition On Liver From The "Second Hit" Caused By The Critical Diseases & The Detection Of The Hepatic And Intestinal Function

Protective effect of the early enteral nutrition on liver from the "second hit" caused by the critical diseases & the detection of the hepatic and intestinal functionObjective To investigate the mechanism of the protective effect of the early enteral nutrition on liver from the "second hit" injury caused by the critical diseases and choice the sensitive indicators of the liver function, the influence of enteral nutrition on the rats with critical disease was evaluated.Methods The model of "second hit" caused by haemorrhagic shock with lipopolysaccharide peritonitis and enteral or parenteral nutrition was made in rats. The rats were divided into three groups including enteral nutrition group (EN Group), parenteral nutrition group (PN Group) and combined nutrition group (enteral and parenteral nutrition, EPN Group). Enteral or parenteral nutrition were started at 0h, 6h, 12h, 24h & 7d post model was created in EN and EPN Group. Parenteral nutrition was given 12h & 7d after operation in PN group. Nutrition had been continued for 5 days for each group. There were 6 rats in each Sub-group. Blood was taken on 1st, 3rd & 5th (7th, 10th, 12th) day for biochemical study. The rats were sacrificed on 5th (12th) day and the liver & small intestine had been porcument for further investigation. The bacteria translocation through intestinal barrier was inspected by microbiology culture and the LPS determination. The high expression of TLR4 protein was detected via immunohistochemistryResults1 Hepatic serology indicators had been referenced, including nutriture indicators (TP, ALB, TRF, PA & RBP); the hepatocellular necrosis indicators (ALT, AST, ADA & TBA) and bile duct obstruction indicators (GGT & ALP).1.1 Comparison among 4 nutrition-supplied time sub-groups: ①Group EN: RBP in Sub-group EN2, EN3 & EN4 on 5th day increased significantly with that in EN1 (P＜0.05); while AST decreased significantly(P＜0.05). ALT for EN2 & EN3 on 3rd & 5th day showed significant lower than that in EN1, same indicator in EN2 on 5th day is lower than that in EN4(P＜0.05); ADA for EN2 & EN3 on 1st showed lower significantly than that in EN4; ALP for EN3 & EN4 on 3rd & 5th day had significant difference with that in EN1 (P＜0.05).②Group EPN: The significant difference of RBP was detected in Sub-group EPN2 & EPN3 on 1st day with that in EPN4; and same indicator in EPN2 & EPN3 on 3ra & 5th was higher than that in EPN1, and for EPN2 was higher than that in EPN4(P＜0.05). ADA on 3rd day in EPN2 & EPN3 was lower than EPN1 (P＜0.05).1.2 Comparison among 3 nutrition-supplied groups:①0 hour post-operation (Sub-group EN1, EPN1, PN1): AST, ALT, GGT & ALP in Sub-group EN1 and/or EPN1 on 3rd & 5th were lower than Group PN1 (P＜0.05).②6 hours post-operation (Sub-group EN2, EPN2, PN1):AST, ALT, ADA, TBA, GGT & ALP in Sub-group EN2 & EPN2 on 3rd & 5th day were lower than Group PN1 (P＜0.05); no obvious change for other indicators relating to nutrition aspects, except for RBP on 5th day in EPN2 was obviously higher than EN2 & PN1(P＜0.05).③12 hours post-operation (Sub-group EN3, EPN3, PN1): Similar to the result of②, only ADA & GGT on 5th day in EPN3 were lower than EN3 (P＜0.05); RBP in EN3 & EPN3 on 5th increased significantly with Group PN1(P＜0.05).④24 hours post-operation (Sub-group EN4, EPN4, PN1): AST, ALT,ADA,TBA,GGT &ALP in EN4 & EPN4 on 5th day is decreased significantly with that in PN1(P＜0.05); while RBP showed the opposite trend(P＞0.05).⑤7 day post-operation (Sub-group EN5, EPN5, PN2): TP, PA& RBP are increased 10th and 12th day in EN5 & EPN5 comparing with PN2 (P＜0.05), while ALT, AST, ADA, TBA & ALP have the opposite trends in the same group(P＜0.05).2 Weight declining:①Each of Group presented phenomenon of weight declining after surgery. Within Group EN, the reducing of weight in EN1 is more obvious than other 3 sub-groups (P＜0.05); within Group EPN, there is not much weight declining difference between sub-groups (P＞0.05).②Comparison among 3 nutrition-supplied groups: no difference among EN1, EPN1 & PN1 (P＞0.05); while compare between Sub-group EN2-4, EPN2-4 with Group PN1, sample weight in Group PN1 has been reduced significantly(P＜0.05).Same result also showed in PN2 with EN5 & EPN5.3 Bacterial translocation (BT) ratio & LPS in portal vein inspection:①Comparison between Group EN & EPN: no difference in BT ratio & LPS density among the former 4 different sub-groups (P＞0.05).②Comparison between 3 nutrition-supplied groups: to compare between EN2-4, EPN2-4 with PN1, BT ratio & LPS determination had increased significantly in Group PN1 (P＜0.05). BT ratio was 100% in EN5, EPN5 &PN2, LPS determination was higher in PN2 than that of in EN5 & EPN5 (P＜0.05).4 Result of immunohistochemistry presented:①"second hit" caused serious damages to liver and intestine. The hepaticellur was mass necrosis. The intestinal mocosa epithelium was necrosis.②Group EN, EPN showed compensatory proliferation happened.Group PN showed little recovery.③TLR4 showed expression in the Kuffer cell in liver and mononulearcell in the intestinal mocosa.④TLR4 protein showed high expression in Group PN comparing with EN& EPN.Conclusion1 The experimental has proved that serious damage has resulted to liver under the Second Hit from perspectives of biochemistry, bacteriology & pathology.2 EEN support has effectively reduced the damage and to certain extent facilitate the recovery of liver function.3 Comparison of 3 nutrition-supplied ways:①Impact to nutrition: acceptance of Group EN and EPN is better, relatively less reduction of weight, no EN complications; weight of Group PN has been reduced significantly, with the phenomenon of losing fur.②Impact to liver function: protection result to Group EN & EPN is better than Group PN, namely the indicators relating to the system nutrition, relating to the hepatocellular necrosis & bile duct obstruction have either reduced or improved markly.③Impact to intestines barrier function: result in Group EN & EPN is better than Group PN in terms of preventing intestines bacterial translocation. So we can draw a conclusion that EN is more effective than PN, while compounded nutrition is not better than single EN.4 Best timing to nutrition support:①In Group EN, there is no result difference in terms of nutrition aspect among EN2-4; while indicators relating to liver hepatocellular necrosis presented best result in EN2 & EN3, indicators relating to bile duct obstruction presented best result in EN3. In Group EPN, there is no obvious difference between results among EPN2-4, while indicators changing between the three experimental point (1st, 3rd & 5th day post operation) has been most obviously in EPN3. Therefore conclusion of providing nutrition at the 12th hour post-operation shall be the best choice, which means EN supplying shall be most effective at this time.②Immediate nutrition support post surgery (EN1 & EPN1) cannot provide ideal result in terms of life condition and each of indicators. And life condition & key indicator result for group with nutrition support at 6th hours post surgery are quite satisfactory, which proves that once anaesthesia period overcame, stomach-intestine movement recovered, EN supply is safety.5 Group EPN has no difference with Group EN; which implies only EN is effective, the radio of calorie & nitrogen supplied by EN to all nutrition supplied ways has no connection with the clinical effect, which explains quantity does not impact the result.6 Early enteral nutrition is better than late enteral nutrition. The outcomes of Group EN1-4, EPN1-4 & PN1 are better than Group EN5, EPN5& PN2.7 Sensitive biochemistry indicators : RBP is better than indicators of TRF, PA & ALB. ALT is the golden indicator relating to cytonecrosis. Comparing with ALT, ADA is always more sensitive in reflecting the hepatic function recovery results.