| Background: The Cachexia may be defined as reduced carcass weight and cause the death of the cancer patients. It is a complex syndrome presenting anorexia, weight loss, wasting of muscle and adipose tissues, hyperlipidemia, and other metabolic abnormalities, usually seen at an advanced stage. The function of intestinal mucosa structure and barrier function is very important for the cancer cachexia patients. Cancer cachexia may initiate a cascade of intestinal events such as intestinal cytokine response, increased intestinal permeability, translocation of intestinal bacteria and endotoxin, leading to systemic inflammatory response syndrome (SIRS) and sepsis with subsequent multiple organ failure. The pro-inflammatory cytokines play a important role in the mechanism of the intestinal dysfunction besides the inducer of anorecxia. an elevated resting energy expenditure and chemotherapy or radiotherapy. Cytokines, such as TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) have been proposed as causative factors of inducing the breakdown of the tight junction of the intestinal mucosa or the apoptosis of the intestinal mucosa cells. Studies of the cytokine network involved in cachexia intestinal mucosa structure and barrier function continue to be a major area of research.The cytokines are divided by function to two groups: (1)the promoter of the malnutrition: TNF, IL-1. IL-6 INFγ, LIF;(2)the inhibitor of the malnutrition: sTNFR, IL-1 receptor, IL-4 , IL-10, IL-13, IL-15. TNF play a center role in all the cytokines. TNF-alpha is a 17-kDa proinflammatory cytokine produced mainly by mononuclear cells. Recent studies have shown TNF-alpha to play a central role in the intestinal inflammation. The TNF- alpha levels are markedly elevated in patients with intestinal inflammation disease including in serum, stool, and intestinal tissue. The increased levels of TNF- alpha lead to increased production and activation of other proinflammatory cytokines and factors that promote intestinal inflammation. The central importance of TNF- alpha in intestinal inflammation has been well validated by clinical studies that show anti-TNF- alpha antibody to be an effective agent in the treatment of active intestinal inflammation. Consistent with the clinical studies, anti-TNF- alpha antibody has also been shown to be effective in the treatment of animal models of intestinal inflammation. In addition to activating the endogenous inflammatory cascade, a potential proinflammatory action of TNF- alpha includes thealteration of intestinal epithelial TJ barrier and mucosa cell apoptosis. TNF- alpha has been shown to produce an increase in epithelial TJ permeability in various cell types, including in intestinal epithelial cells. Thus elevated TNF- alpha levels could be an important factor contributing to the intestinal TJ permeability defect and apoptosis in patients. The intracellular mechanisms involved in TNF- alpha modulation of intestinal TJ barrier remain unclear. Understanding the intracellular mechanisms involved could be important in devising future therapeutic strategies to induce retightening of the leaky TJ barrier.Development of profound intestinal mucosa structure and barrier function in cancer cachexia patients has aroused the interest of researchers for many years, and extensive studies have been undertaken in attempts to elucidate the mechanisms behind this ill-defined state and to reverse it. The purpose of this study was to investigate the relation of intestinal mucosa structure and barrier function with cytokines and observe function of celecoxib and glutamine with the protection of intestinal mucosa of the cancer cachexia patients.Part 1 The relation between alterations of intestinal mucosa structure andbarrier function with cytokines factor with cancer cachexia mice14 male BALB/c mice were randomized into two groups: control group and tumor-bearing group. For tumor-bearing group, a suspension of 106 murine colon 26 adenocarcinoma cells was inoculated s.c into each mouse. Non-tumor body weight, intestinal villus height, width, basal layer width and muscular layer width, TNF-alpha,IL-1,11-6,11-10,IFN-gamma,sTNF-R I and sTNF-R II in the serum and intestinal tissue were determined at the 16th day following the inoculation and the gene of TNF and TNF-RDD were also tested by RT-PCR. Results: The Non-tumor ?body weight and intestinal villus height and basal layer width were lost significantly as compared with control group[(25.429± 1.397)g vs(15.57± 1.618)g, (222.66± 43.47) urn vs (93.18 + 8.34) u m,(52.32±7.31) u m vs (48.33 ± 4.88) u m]. Also the concentration of serum TNF-alpha,IL-6,sTNFR I , IL-10 were changed markedly between the two groups [(11.43±6.29)pg/ml vs (19.43 + 7.09) pg/ml,(4.57±0.28) pg/ml vs (2120.57 + 321.91) pg/ml,(l349.62 + 366.99) pg/ml vs (675.81 ±40.45) pg/ml,(44.00±2.83) pg/ml vs (4.00 + 0.26) pg/ml].The concentration of intestinal tissue TNF-alpha, IL-lJFN-gamma, sTNFR I , sTNFRU were changed markedly between the two groups[ (0.29±0.09) pg/ml vs (2.86 + 0.79) pg/ml, (141.86 + 14.75) pg/ml vs (53.29 + 6.97) pg/ml, (0.29±0.075) pg/ml vs (7.43 ±0.60) pg/ml, (54.34±5.82) pg/ml vs (13.64+1.07) pg/ml, (3.91+0.79) pg/ml vs (1.29 + 0.35) pg/ml]. the tumor bearing group have a high TNF and TNF-RDD gene expression than the control group significantly.Part 2 Effects of celecoxib and glutamine on intestinal mucosa structure and barrier function in cancer cachexia miceTwenty-eight male BALB/c mice were divided randomly into four groups: A, tumor-bearing; B, tumor-bearing plus celecoxib (20mg/kg); C, tumor-bearing plus glutamine (20mg/kg); D, tumor-bearing plus celecoxib (20mg/kg) and glutamine (20mg/kg). Colon 26 adenocarcinoma cells of murine were inoculated subcutaneously to induce cancer cachexia. Celecoxib and glutamine were given orally daily for 16 days from the onset of cachexia to sacrifice. The data was collected as part 1 listed before. Results: In the celecoxib group, the body weight and intestinal villus height TNF-alpha and IL-6 in blood and IFN-gamma in intestinal tissue were changed significantly as compared with control group [(15.57+1.62 vs 23.00±2.16)g, (93.18 ±8.34 vs 146.79 ±36.88) urn, (19.43 ±7.09 vs 16.00 ±2.53)pg/ml, (2210.57 + 321.91 vs 830.00±56.43)pg/ml, (0.29 + 0.08 vs 3.17+0.71)pg/ml]. In the glutamine group, the body weight and intestinal villus height TNF-alpha, IL-6 and IL-10 in blood and IFN-gamma in intestinal tissue were changed significantly as compared with control group [(15.57+1.62 vs 21.86±1.22)g, (93.18±8.34 vs 245.65±29.50) um, (19.43±7.09vs 14.40±9.2l)pg/ml, (2210.57 + 321.91 vs 113.60 + 58.35)pg/ml. (44.00 ±4.83 vs 76.18 ± 7.35)pg/ml, (0.29 ±0.08 vs 9.43 ± 1.83)pg/ml]. In the celecoxib and glutamine group, the body weight and intestinal villus height TNF-alpha, IL-6, IL-10 and sTNFR I in blood and IFN-gamma in intestinal tissue were changed significantly as compared with control group [(15.57+; 1.62 vs 22.83± 1.33)g, (93.18±8.34 vs 232.01 + 37.36) u m, (19.43±7.09 vs 4.50±0.58)pg/ml. (2210.57±321.91 vs 31.5±3.74)pg/ml, (1349.25±366.99 vs 337.12±23.07)pg/ml. (44.00±4.83 vs 65.70±2.99)pg/ml, (0.29±0.08 vs 11.12±2.31)pg/ml.Part 3: The dependability of intestinal permeability and inflammatory reaction in gastric cancer patientsThirty stomach cancer patients were enrolled in the study. Lactulose/mannitol test was performed on the day of hospitalization. The patients were retrospectively analyses with Inbody 3.0, ( Biospace Co.) and automatic biochemistry analyzer for BMI FFMI BFMI ALB PA FN TF LC IBW%, observe the relation between L/M and nutritional index. Results: L/M ratio of control group was 0.028±0.01, and the undernutrition group was 0.161±0.141 respectively, significant difference of L/M ratios were found between two groups. The ALB and IBW% and BFMI changed significantly in high L/M ratio group [(29.900±1.835 vs 41.193±3.807) (22.257±11.225 vs 25.920±5.951) (5.586±3.681 vs 3.419±1.889)]. The CRP changed significantly in high L/M ratio group (5.69 vs 17.40).ConclusionThe intestinal villus height and basal layer width of C26 cancer cachexia mice changed significantly. The intestinal permeability of C26 cancer cachexia mice...
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