| ObjectiveGallstone is a global common disease, incident rate of which is about 10 %. Biopsy found out that the morbidity of cholelithasis in western countries was 5% to 25%. What is more, 70% to 80% of it was cholesterol gallstone. In China the incident rate also varied in different places. For example, in Shanghai the majority of cholelithasis was mixed cholesterol gallstone. In recent years, the ratio of cholesterol gallstone in our country has been rising because of the alternation of diet composition and the increase of animal fat intake. How to prevent and treat cholelithasis has been a concerning problem nowadays. The pathogenesis of cholelithasis has not been clarified yet. Besides the common factors such as cholesterol superaturation, biliary protein, biliary salt enterohepatic circulation and gallbladder motility, Chronic inflammatory may also been concerned about.Cyclooxygenase (COX) or prostaglandin endoperoxide synthase (PGHs) isrequired for the conversion of arachidonic acid to prostaglandins, catalyzes the first step of the synthesis of prostanoids. Two isoforms of this enzyme have been identified which are referred to as COX-1 and COX-2. COX-1 is constitutively expressed as a "housekeeping" enzyme in most tissues such as endothelial and smooth muscle. By contrast, COX-2 can be induced by various several physiological stimuli and pro-inflammatory agents, including lipopolysaccharide (LPS), cytokines, and growth factors. And it is up-regulated at sites of inflammation.Several studies have demonstrated that Specific inhibitor of cyclooxygenase type 2 (COX-2) inhibits prostaglandin synthesis much like conventional NSAID. It can have antiinflammatory and antialgesic activities without affecting prostaglandin synthesis at sites where classical NSAID have known toxicity. NSAIDs can reduce the risk of cholesterol gallstone formation by inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic, and antipyretic effects. However, many of the side effects of NSAIDs (e.g., gastrointestinal ulceration and bleeding, platelet dysfunctions) that caused by a suppression of COX-1 activity occurs. It suggested that specific COX-2 blocker may offer an alternative to traditional NSAIDs with fewer side effects. Certain study showed that specific COX-2 inhibitor is involved in the inflammatory response during chronic cholecystitis. Specific blockage of COX-2 reduced the PGE2 release to the inflamed gallbladder lumen. Whether specific COX-2 inhibitor could reduce the risk of cholesterol gallstone formation by inhibitor anti-inflammatory effects raised our interest.The present study aimed to demonstrated the effect of specific COX-2 inhibitor on gallbladder during lithogenic process by investigated the change of mucosa inflammatory, COX-2 expression and cholesterol crystal formation in rabbit models, which were induced by high cholesterol diet (HCD) and certain group of which was interfered by specific COX-2 inhibitor(Celecoxib).MethodA total of 30 rabbits of either sex (3-4months old, 2.2 - 2.9kg) were divided into three groups at random : gallstone group (induced by high cholesterol diet, HCD, n=10), Celecoxib group(treated with Celecoxib 10mg·kg-1·d-1 in addition to HCD, n=10) ,and control group(fed with formal diet, n=10). These three groups were fed with formal diet for one week, following with specific diet. After 7 weeks, 12-hour-fasted animals were killed. Cholecystectomy was performed. The bile was collected for observing the gallstone formation. A 2mm × 2 -4mm tissue was lognitudinaly cut for morphologic observation and immunohistochemical stain in each gallbladder.The bile was judged glossly to determine whether there was sandy crystal (D>1mm). The specimens from gallbladder were preserved in 10% formalin, embedded in paraffin, sectioned onto microscope slides at a thickness of 5um. Pathologic diagnosis was based on hematoxylin and eosin stain (H-E stain).Tissue immunohisochemical staining was done with Ultra Senstivie S-P Kit. The slides were deparaffi...
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