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Effect Of Emodin On Plasma Albumin, TNF-α, IL-6 Level In Peritoneal Sepsis Rat

Posted on:2007-02-23Degree:MasterType:Thesis
Country:ChinaCandidate:K R WuFull Text:PDF
GTID:2144360182487398Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background and purpose:Intra-abdominal infection is a common problem in surgery. Severe intra-abdominal infection is one of the most causes of systemic inflammatory response syndrome (SIRS) or sepsis. Once SIRS or sepsis arises, it will be very difficult to cure and the mortality will be greatly increased. Severe sepsis, which occurs in about 750,000 people in the United States every year, carries a mortality rate close to 30%. It is generally believed that SIRS is characterized by infectious or non-infectious factors causing a persistant and generalized inflammatory reaction including liberation of large amount of cytokines and other inflammatory mediators and subsequent pathophysiological alterations. Many efforts have been made to block up the inflammatory response in the last ten years, but the result is not satisfactory .Rhubarb is a kind of traditional Chinese herbal medicine. It has been used clinically for several thousand years. Pharmacologically, Rhubarb has the functions as laxative for indigestion, antipyretic for detoxication, and cooling blood against stasis. It is believed that rhubarb has significant effect on treating SIRS and multiple organ dysfunction syndrome (MODS). Liu Ruilin et al showed that emodin may depress the release of cytokines and ameliorate the inflammatory response of acute necrotic pancreatitis in rat. But the protective effect of emodin on peritoneal sepsis in rat has not been mentioned.Emodin was administered intravenously and by comparing he plasma albumin, TNF-a, IL-6 andintestinal mucosa pathological grade of rats, the protective and therapeutic effects of emodin on peritoneal infected animal were observed. The mechanisms are further discussed.Materials and methods:90 healthy and matured male Sprague-Dawley (S-D) rats, weighing 180-230 g, provided by the animal center of Zhejiang Chinese traditional medical college were used. Animals were divided into three groups randomly (group A, B and C). There were 30 rats in every group. All animals were fasted for 12 h before the experiment, but with water ad libitum. 3% pentobarbital sodium solution were administered intraperitoneally in animals with the dosage of 45 mg/kg. And then the abdomen was opened in the mid-line, caecum was found and one third of caecum were ligated to avoid obstruction and punctured with 18# needle in group B and C to leak small amount of intestinal content into the peritoneal cavity causing peritoneal infection. After that, the caecum was put back to the abdominal cavity, and the abdomen was closed. No caecal ligation and no puncture were done in group A. All animals took food ad libitum postoperatively.After operation, rats in group B were given emodin 10 mg/kg diluted with 2 ml water injected into caudal vein ql2 h. Rats in group C were given 2 ml water iv q 12 h as control. Different groups of animals (n=10 per group) were studied 12, 24 or 36 h after operation, animals were anesthetized, blood was taken from the vena cava and then intestinal biopsy were taken. Blood were centrifuged at 3000 rpm/min for 10 min after 30 min interval, plasma were taken and stored at -70°C. The specimens were fixed in 10% formaldehyde. The general condition of rats such as mental condition, activity, appetite and stool were observed.Plasma albumin levels were assayed by BCG automating analysis. Plasma concentrations of TNF-a and 1L-6 were determined by enzyme-linked immunosorbent assay (ELISA).Pathology: The specimens of resected intestinal were embedded in the paraffine. The sample was dyed with HE stain and observed through optics microscope, the mucosal changes are graded .The data was analysed with Student-Newman-Keuls Test or Kruskal Wall is Test by SPSS 10.0 software package. If the variance was not uniform, the transformation of variable would be made touniform the variance and then the analysis of variance was made as above.Result:All 90 rats survived during the experiment. After operation the majority of rats in group B and C gradually depressed, movement and appetite decreased. Most rats in group B had diarrhea. Most rats in group C had mucous and fewer stool.Plasma albumin in group B is significantly higher than that in group C 36 h after operation (p<0.05).Plasma TNF-a concentration in group B is significantly lower than that in group C at 12 h, 24 h and 36 h after operation (p<0.05, p<0.05, p<0.01).Plasma IL-6 concentration in group B is significantly lower than that in group C at 24 h and 36 h after operation (p<0.05, p<0.05).The abdominal cavity of rats in group B and C had purulent or bloody secretion with foul swelling. Intestine distended. Viscera congested and edematous.Through optic microscope we can find that the lesion seen in the intestinal mucosa is the development of subepithelial spaces near the tips of the villi in group B 12 h after operation. At the same point , extension of the subepithelial space with moderate lifting of epithelial layer from the lamina propria can be seen in group C. At 24 h after operation, extension of the subepithelial space with moderate lifting of epithelial layer from the lamina propria can be seen in group B whereas massive epithelial lifting down the sides of villi and a few tips may be denuded in group C(p<0.017, group B versus group C). At 36 h after operation, massive epithelial lifting down the sides of villi and a few tips may be denuded, denuded villi with lamina propria and dilated capillaries exposed in group B. Increased cellularity of lamina propria may be noted in group C(p<0.017, group B versus group C).Conclusion:Emodin administered iv can significantly reduce the level of TNF-a and IL-6 and improve theconcentration of plasma albumin and reduce the intestinal mucosa damage. In conclusion, emodin is good for peritoneal sepsis in rat. The blocking up the damage of intestinal mucosa may be the way emodin works.
Keywords/Search Tags:albumin, cytokine, sepsis, emodin, IL-6, systemic inflammatory, response syndrome, TNF-α
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