Tumor-derived semaphorin 3D promoting cancer cachexia via regulating hypothalamic pro-opiomelanocortin neurons.

Cachexia is very common in cancer patients and predicts a poor prognosis; however, the molecular basis for progress in these individuals remains unclear, especially the effect of tumors on the hypothalamus energy regulation center. To investigate the regulatory pathway of tumors associated with hypothalamic pro-opiomelanocortin (POMC) neurons known as appetite-inhibiting neurons, we conducted observations both on patients and mice models. Results showed that the highly expressed exocrine semaphorin 3D (SEMA3D) both in cachexia patients and mice was positively related to the expression of POMC and its proteolytic peptide. Compared with the control group, mice inoculated with the SEMA3D-knockout C26 cell line decreased the activity of POMC neurons resulting in a 1.3-fold increase in food intake, a 22.2% increase in body weight, and reduced skeletal muscle and fat catabolism. The effect of SEMA3D on cachexia progression can be partially alleviated by knocking-down POMC expression in the brain. In terms of mechanism, SEMA3D enhances the activity of POMC neurons by activating the expression of NRP2 (membrane receptor) and PlxnD1 (intracellular receptor). Our research revealed the overexpression of SEMA3D in tumors works as an activator of POMC neurons, which may play a vital role in suppressing appetite and promoting catabolic metabolism.

Oral nutritional supplements, physical activity, and sarcopenia in cancer.

PURPOSE OF REVIEW: Sarcopenia is prevalent in cancer patients and can occur as a result of cancer as well as cancer-related therapies. It is related to high postoperative complications, long hospitalization, slow recovery as well as low tolerance to chemotherapy. Patients with sarcopenia also have poor oncological outcomes. Oral nutritional supplements (ONS) and physical activity have shown great potentials in managing this debilitating condition. We summarized the recent developments in the assessment of sarcopenia and its management with ONS and physical activity. RECENT FINDINGS: Many methods were developed to evaluate sarcopenia including muscle quality/quantity measurement and functional tests. Recent studies have shown that ONS and physical training can be used in managing sarcopenia, especially when used together as part of a multimodal intervention. However, barriers such as low awareness and lack of training and support for both patients and healthcare workers still exist and need attention. SUMMARY: Recent findings highlighted the benefits of identifying sarcopenia and managing those at risk. The details of a multimodal protocol, such as components of nutritional substrates, the intensity of physical exercise, and the use of medication need to be further looked into for an optimum approach. Education and training programs need to be developed to overcome the barriers in managing sarcopenia.

Post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial.

BACKGROUND & AIMS: Malnutrition frequently occurs and deteriorates in patients after surgery for gastric cancer, especially after hospital discharge, which has been consistently associated with negative outcomes. However, information regarding the impact of post-discharge nutritional interventions is poorly described. The aim of this study was thus to evaluate the impact of post-discharge oral nutritional supplements (ONS) with dietary advice compared with dietary advice alone on nutritional outcomes, including body mass index (BMI) and skeletal muscle index (SMI), sarcopenia prevalence, chemotherapy tolerance, the 90-day readmission rate, and quality of life in patients at nutritional risk after surgery for gastric cancer. METHODS: Three hundred and fifty-three patients who underwent surgery for gastric cancer and were at nutritional risk (Nutritional Risk Screening 2002 [NRS 2002] score ≥3 points) in our institution were randomly assigned to receive either ONS with dietary advice or dietary advice alone (control) for 3 months after discharge. The primary endpoints were nutritional outcomes and sarcopenia prevalence; the secondary endpoints included chemotherapy tolerance, the 90-day readmission rate, and quality of life. RESULTS: Three hundred and thirty-seven patients completed the study and were included in the analyses, consisting of 171 in the ONS group and 166 in the control group. The average daily intake of ONS in the intervention group was 370 mL. After 3 months of the intervention, the patients who received ONS and dietary advice had significantly less weight loss and higher BMI and SMI than those given dietary advice alone (P < 0.05). The incidence of sarcopenia was significantly lower in the ONS group than in the control group (P < 0.05). Similar number of patients in the two groups underwent postoperative chemotherapy, but the patients who received ONS and dietary advice had significantly less chemotherapy modifications, including delay, dose reduction, or termination (P < 0.05). The two groups had no significant differences in the 90-day readmission rate (P > 0.05). Regarding the quality of life, the patients who received ONS and dietary advice reported significantly less fatigue and appetite loss than those given dietary advice alone (P < 0.05), but the two groups showed no significant differences in the other outcomes (P > 0.05). CONCLUSIONS: Post-discharge ONS with dietary advice in patients at nutritional risk after surgery for gastric cancer improved nutritional outcomes, skeletal muscle maintenance, chemotherapy tolerance and some quality of life variables. These findings strongly support the concept of the introduction of post-discharge ONS with dietary advice to this patient cohort.

Impact of oral nutritional supplements in post-discharge patients at nutritional risk following colorectal cancer surgery: A randomised clinical trial.

BACKGROUND & AIMS: Guidelines on clinical nutrition recommend the use of appropriate nutritional support therapy for surgical cancer patients at risk of malnutrition both during hospital care and following discharge from the hospital. However, previous studies regarding nutritional interventions have mainly focused on patients during their hospital stay; there is limited evidence supporting the recommendation of nutritional interventions for post-discharge patients after cancer surgery, particularly those who underwent gastrointestinal cancer surgery and at high risk of malnutrition. To clearly address this issue, we designed and conducted two independent studies on two different groups of post-discharge patients at nutritional risk after gastrointestinal cancer surgery. The present study aimed to assess the impact of oral nutritional supplements (ONS) in post-discharge patients at nutritional risk following colorectal cancer surgery. Meanwhile, the sister study on the use of ONS in post-discharge patients following gastric cancer surgery will be reported separately. METHODS: Between January 2017 and June 2019, post-discharge patients following colorectal cancer surgery in our institution were randomised to receive either dietary advice alone (control group) or dietary advice in combination with ONS (ONS group) for three months if they were at nutritional risk based on the tool of Nutritional Risk Screening 2002. The primary endpoints were nutritional outcomes and sarcopenia prevalence. The secondary endpoints were 90-day readmission rate, chemotherapy tolerance, and quality of life (QoL). RESULTS: Of the 232 eligible patients, 212 (107 in the control group and 105 in the ONS group) completed the trial. Their data were then analyzed. The mean ONS intake was 410 mL every day. By the three-month intervention, the skeletal muscle index in the ONS group was significantly higher than that in the control group (39.75 ± 5.83 vs 38.01 ± 6.18 cm2/m2, P = 0.037), but no significant differences between the two groups were noted in weight, weight loss, body mass index, serum albumin and hemoglobin (P > 0.05). In addition, the ONS group had a significantly lower sarcopenia prevalence (28.6% vs 42.1%, P = 0.040). No significant difference between the two groups was found in the 90-day readmission rate (P > 0.05). The number of patients undergoing postoperative chemotherapy in the two groups was similar, but chemotherapy modifications, such as delay, dose reduction, or termination, were significantly reduced in the ONS group (21.2% vs 36.8%, P=0.024). However, ONS had no significant effect on QoL (P > 0.05). CONCLUSIONS: In post-discharge patients at nutritional risk following colorectal cancer surgery, the use of ONS may reduce skeletal muscle loss and sarcopenia prevalence, as well as improve chemotherapy tolerance, compared with dietary advice alone. These findings underline the importance of ONS treatment in post-discharge patients at nutritional risk following colorectal cancer surgery.

Efficacy and safety of pectin-supplemented enteral nutrition in intensive care: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Enteral nutrition (EN) can improve clinical outcomes as an important treatment in critically ill patients. However, when patients suffer from gastrointestinal function disorders, intestinal intolerance occurs and EN administration may be delayed and even fails to perform. Pectin, a structural heteropolysaccharide, could protect gastrointestinal function from disorders in many gastrointestianl diseases. The present study aimed to determine whether pectin-supplemented EN was safe and improved clinical outcomes in intensive care unit (ICU) patients. METHODS AND STUDY DESIGN: Patients enrolled in ICU from August 2014 to January 2015 were randomized to EN group and pectin-supplemented EN group (PEC/EN group). Both group received isonitrogenous, isocaloric EN support within 36 hours after ICU admission, and last for 6 days. The primary endpoints were 30-day mortality and gastrointestinal intolerance. RESULTS: There were 125 patients included in this study (63 in EN group, and 62 in PEC/EN group). The results showed that the 30-day mortality was 4.8% in EN group and 1.61% in PEC/EN group (p=0.317). PEC/EN group had a smaller gastrointestinal intolerance rate than EN group (41.3% vs 27.4%, p=0.04). Furthermore, there were shorter times to reach full EN (13.0±5.12 vs 9.99±1.91, p=0.05), length of ICU stay (17.9±9.72 vs 13.8±8.59, p<0.001), and length of hospital stay (32.9±19.0 vs 23.4±13.2, p<0.001) in EN group than those in PEC/EN group. CONCLUSIONS: These results revealed that pectin- supplemented EN was safe, and could improve clinical outcomes in ICU patients.

Lipid-rich enteral nutrition controls intestinal inflammation, improves intestinal motility and mucosal barrier damage in a rat model of intestinal ischemia/reperfusion injury.

BACKGROUND: It has been reported that lipid-rich enteral nutrition (EN) could ameliorate inflammation in various diseases. In this study, we investigated whether lipid-rich EN could control intestinal inflammation, improve intestinal motility and mucosal barrier injury after intestinal ischemia/reperfusion (I/R) injury. METHODS: Male adult rats received saline, conventional EN, or lipid-rich EN via gavage before and after intestinal I/R injury. The superior mesenteric artery was occluded for 60 min. The sham group underwent laparotomy without superior mesenteric artery occlusion and was administrated saline. Intestinal motility was measured 4 h after intestinal I/R injury by fluorescein isothiocyanate-dextran transit assay; the intestinal and systemic inflammation were assessed by analyzing intestinal and serum concentrations of tumor necrosis factor α, interleukin (IL)- 6, and IL-10, separately. The intestinal mucosal barrier injury was assessed by analyzing the serum levels of intestinal fatty acid-binding protein (I-FABP) and intestinal mucosal tight junction (TJ) proteins. RESULTS: The intestinal I/R injury decreased intestinal motility and intestinal mucosal TJs expression significantly when compared with the sham group (P < 0.05). The intestinal and systemic inflammatory parameters and the serum I-FABP were also significantly higher in the I/R groups than those in the sham group (P < 0.05). Both conventional and lipid-rich EN increased the intestinal motility and the intestinal mucosal TJs expression and decreased the intestinal and systemic inflammatory parameter and serum I-FABP levels to different degrees when compared with the I/R group (P < 0.05). However, lipid-rich EN significantly improved the negative alterations in these biochemical parameters when compared with the conventional EN (P < 0.05). CONCLUSIONS: These results suggest that lipid-rich EN might be able to control intestinal inflammation, improve intestinal motility and mucosal barrier injury after intestinal I/R injury. Thus, the administration of lipid-rich EN may be an effective treatment for promoting gastrointestinal function recovery after intestinal I/R injury.

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting.

Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-κB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.

Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

High-fat enteral nutrition controls intestinal inflammation and improves intestinal motility after peritoneal air exposure.

BACKGROUND: Peritoneal air exposure is a common phenomenon in abdominal surgery, but long-term exposure could induce intestinal inflammatory responses, resulting in delayed recovery of gastrointestinal motility after surgery. High-fat enteral nutrition has been reported to ameliorate inflammation in many diseases. In the present study, we investigated whether high-fat enteral nutrition could control intestinal inflammation and improve intestinal motility after peritoneal air exposure. METHODS: Male adult rats were administrated saline, low-fat enteral nutrition, or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Control rats underwent anesthesia without laparotomy and received saline. Intestinal motility was assessed 24 h after surgery by charcoal transport assay; systemic inflammation was assessed by analyzing serum levels of tumor necrosis factor α, interleukin (IL)-1ß, IL-6, and IL-10; and intestinal inflammation was assessed by analyzing myeloperoxidase activity and concentrations and gene expression of tumor necrosis factor α, IL-1ß, IL-6, and IL-10 in the intestinal tissue. RESULTS: Peritoneal air exposure decreased intestinal motility significantly compared with the control group (P < 0.05). The systemic and intestinal inflammatory parameters were also much higher in the peritoneal air exposure groups than in the control group. Both low-fat and high-fat enteral nutrition increased intestinal motility and reduced systemic and intestinal inflammatory parameter levels to different degrees. However, high-fat enteral nutrition significantly improved the negative alterations in these biochemical parameters compared with low-fat enteral nutrition (P < 0.05). CONCLUSIONS: These results suggest that high-fat enteral nutrition might be able to control intestinal inflammation and improve intestinal motility after peritoneal air exposure. Thus, the perioperative administration of high-fat enteral nutrition may be a promising treatment to enhance the recovery of intestinal motility after surgery.

Peri-operative immunonutrition in patients undergoing liver transplantation: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: No consensus has been reached concerning the effects of peri-operative immunonutrition in patients undergoing liver transplantation. We conducted a meta-analysis to evaluate the effects of peri-operative immunonutrition on clinical outcomes and liver function in patients undergoing liver transplantation. METHODS AND STUDY DESIGN: The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and google scholar were searched to identify all available randomized controlled studies which compared peri-operative immunonutrition support (glutamine, ω-3 polyunsaturated fatty acids, arginine and ribonucleic acids) with standard nutrition. The data analysis was performed using Revman 5.2 software. RESULTS: A total of 7 randomized controlled trials (RCTs) involving 501 patients were included. Peri-operative immunonutrition significantly reduced the risk of infectious complications (RR: 0.51; 95% CI: 0.27 to 0.98, p=0.04) and shortened the postoperative hospital stay [weighted mean difference (WMD): -3.89; 95% CI: -7.42 to -0.36; p=0.03]. Furthermore, perioperative immunonutrition improved liver function by decreasing the levels of aspartate aminotransferase (AST) in the blood (WMD: -25.4; 95% CI: -39.9 to -10.9, p=0.0006). However, we did not find statistically significant differences in serum alanine aminotransferase (ALT), total bilirubin (TB) and direct bilirubin (DB) levels. There were no statistically significant differences in mortality and rejection reaction. CONCLUSIONS: Peri-operative nutrition support adding immunonutrients like glutamine, ω-3 polyunsaturated fatty acids, arginine and ribonucleic acids may improve outcomes in patients undergoing liver transplantation. Due to the limited sample size of the included trials, further large-scale and rigorously designed RCTs are needed.

Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats.

OBJECTIVES: Septic patients always develop muscle wasting, which delays the rehabilitation and contributes to the increased complications and mortality. Previous studies have implied the crucial role of central inflammation and neuropeptides in the energy balance and muscle metabolism. Insulin has been confirmed to attenuate muscle degradation and inhibit inflammation. We tested the hypothesis whether insulin ameliorating muscle wasting was associated with modulating hypothalamic inflammation and neuropeptides. DESIGN AND SUBJECTS: Thirty-two adult male Sprague-Dawley rats were in intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by subcutaneous injection of insulin (5 IU/kg) or saline. Twenty-four hours after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also measured in four groups. RESULTS: LPS injection led to significant increase in hypothalamic inflammation as well as muscle wasting. Also, increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were observed. Insulin treatment ameliorated endotoxaemia-induced muscle wasting and hypothalamic inflammation, and attenuated the alteration of neuropeptides, POMC, CART and AgRP. CONCLUSION: Hypothalamic inflammation and neuropeptides are involved in the endotoxaemia-induced muscle wasting. Insulin treatment can reduce muscle wasting, which is associated with reduced hypothalamic inflammation and alteration of hypothalamic neuropeptides.

Berberine ameliorates intestinal mucosal barrier damage induced by peritoneal air exposure.

Berberine, an isoquinoline alkaloid derived from many medicinal plants, has been extensively used to treat various gastrointestinal diseases. In the present study, we investigated whether berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure for 3 h. Peritoneal air-exposure rats received 100, 150, and 200 mg/kg berberine orally via gavage four times before and after surgery. Blood and terminal ileum samples were collected 24 h after surgery. The serum D-lactate levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein isothiocyanate (FITC)-dextran (FD4). Intestinal inflammation was assessed by measuring myeloperoxidase activity. Intestinal histopathology was also assessed. The results revealed that berberine decreased the serum D-lactate level, intestinal FD4 clearance, and myeloperoxidase activity. Edema and inflammation were reduced by berberine in the intestinal mucosa and submucosa, and the Chiu's scores, indices of intestinal mucosal injury, also decreased in the berberine-treated group. In addition, berberine exerted these protective effects in a dose-dependent manner, with a significant difference from the control group at doses of 150 and 200 mg/kg. The results suggest that berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure, which is linked to its anti-inflammatory activity. Berberine may be a promising treatment for intestinal mucosal barrier damage in open abdominal surgery.

Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats.

In critical patients, sepsis-induced muscle wasting is considered to be an important contributor to complications and mortality. Previous work mainly focuses on the peripheral molecular mechanism of muscle degradation, however little evidence exists for the role of central nervous system in the process. In the present study, we, for the first time, characterized the relationship between muscle wasting and central neuropeptide changes in a septic model. Thirty-six adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) or saline. Twelve, 24 and 48 hrs after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methyl-histidine (3-MH) and tyrosine release. Hypothalamic neuropeptides and inflammatory marker expressions were also measured in three time points. LPS injection caused an increase expression of MuRF-1 and MAFbx, and a significant higher release of 3-MH and tyrosine. Hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP) and neuropeptide Y (NPY) presented a dynamic change after LPS injection. Also, hypothalamic inflammatory markers, interleukin-1 ß (IL-1ß) and tumor necrosis factor α (TNF-α) increased substantially after LPS administration. Importantly, the expressions of POMC, AgRP and CART were well correlated with muscle atrophy gene, MuRF-1 expression. These findings suggest hypothalamic peptides and inflammation may participate in the sepsis-induced muscle wasting, but the exact mechanism needs further study.

Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.

Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20 mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-α, IL-1ß, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with significance at doses of 10 and 20 mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis.

Anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection in rat.

Ginsenoside Rb1 (GRb1), one of the principle active ingredients of Panax ginseng, exerts multiple pharmacological activities to fight fatigue. In the present study, we investigate the anti-fatigue effect of GRb1 on postoperative fatigue syndrome (POFS) in a rat model induced by major small intestinal resection. GRb1 (10 mg/kg) was administrated intraperitoneally once daily for 1, 3, 7, and 10 d from the operation day. Anti-fatigue effect was assessed by grasping test and biochemical parameters in blood or skeletal muscle were determined by autoanalyzer or commercially available kits. Transmission electron microscope was applied to observe the ultra microstructure of skeletal muscles. The results revealed that GRb1 significantly enhanced rat maximum grip strength with POFS. Similarly, negative alterations in biochemical parameters (lactic acid, hepatic glycogen, muscle glycogen and malondialdehyde) of POFS rats were improved by GRb1. In addition, GRb1 also increased the activity of lactate dehydrogenase and superoxide dismutase in POFS. No significant differences of levels of blood urea nitrogen and ultra microstructure of skeletal muscles were found between the POFS and GRb1 treatment rats. The potent anti-fatigue effect of GRb1 on POFS might be achieved through improvement of energy metabolism and suppression of skeletal muscle oxidative stress.

[Effects of ginsenoside Rb1 on the oxidative stress in the skeletal muscles of rats with postoperative fatigue syndrome].

OBJECTIVE: To observe the effects of ginsenoside Rb1 (GRb1) on the oxidative stress in the skeletal muscles of rats with postoperative fatigue syndrome (POFS) and to study its anti-fatigue mechanisms. METHODS: The POFS model was established using resection of 70% of mid-small intestine. Ninety-six Sprague-Dawley (SD) rats were screened using grasping test. The rats were randomly divided into the control group, the model group, and the GRb1 treated group (at 10 mg/kg) by the body weight. The maximum grip strength of rats was detected on the 1st, 3rd, 7th, and 10th day after operation, respectively. The contents of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) were detected. RESULTS: Compared with the model group, the maximum grip strength was obviously enhanced on the postoperative day 7 and 10 (P < 0. 05), the MDA content obviously decreased on the postoperative day 3 and 7 (P < 0.05), the SOD activity obviously increased in the GRb1 treated group (P < 0.05). There was no obvious change in the activities of CAT and GSH-PX among the three groups at each time point (P > 0.05). CONCLUSION: GRb1 could reduce the oxidative stress injury in the skeletal muscles, improve the activities of antioxidant enzymes, and enhance the functions of the skeletal muscles in POFS rats, which may be important reasons for fighting against POFS.

[Study on characteristics of energy metabolism in skeletal muscle of rats with postoperative fatigue syndrome and interventional effect of ginsenoside Rb1].

OBJECTIVE: To study characteristics of energy metabolism in the skeletal muscle of rats with postoperative fatigue syndrome (POFS) and the interventional effect of ginsenoside Rb1. METHOD: We chose resection of 70% of the "middle" small intestine as the rat model for POFS. Ninety-six adult male SPF SD rats were randomly divided into the control group, the model group, and the ginsenoside Rb1-treated group by body weight. And then, each group was further randomly divided into four subgroups, according to different postoperative investigated time points, such as postoperative day 1, postoperative day 3, postoperative day 7 and postoperative day 10. So the animals were divided into twelve subgroups (n = 8 in each subgroup). Rats of the control group and the model group were injected intraperitoneally with saline at the dose of 10 mL x kg(-1) one hour before the operation and once a day during the postoperative days. Rats of the ginsenoside Rb1-treated group were administered 10 mg x kg(-1) ginsenoside Rb1 by the same method. The skeletal muscles were sampled on postoperative day 1, 3, 7 and 10. The contents of ATP, ADP, AMP in skeletal muscles were determined by HPLC, and the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase were investigated by colorimetry. RESULT: Compared with the control group, the content of ATP in skeletal muscle of rats of the model group decreased significantly on postoperative day 3 (P < 0.05), while the content of ADP significantly increased on postoperative day 7 and 10 (P < 0.05). The activity of Na(+)-K(+)-AT-Pase decreased on postoperative day 3 and 7 (P < 0.05), and the activity of Ca(2+)-ATPase decreased on postoperative day 7. After supplement of ginsenoside Rb1, on the investigated time points, all the negative changes of the indicators discovered above were significantly adjusted (P < 0.05) in rats of the ginsenoside Rb1-treated group, while no significant differences were investigated. CONCLUSION: During a certain period of postoperative time, the activity of energy metabolism is depressed in the skeletal muscle of rats with POFS, but it can be improved by supplement of ginsenoside Rb1.