AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawl...AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawley rats randomlyreceived colonic irritation by acetic acid from postnatal day8 to d 21 as a visceral hypersensitive model (group H) or byintrarectal saline as a control group (group C). When theybecame adults, rectal distention (RD) was performed by aballoon (6F; Fogarty arterial embolectomy catheter; length,20 mm; diameter, 2 mm) which was rapidly inflated withincreasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 sat five-minute intervals. Five subgroups of group H (H-saline,H-vehicle, H-Teg0.1, H-Teg0.3 and H-Tegl.0) were injectedrandomly with saline, vehicle (1-methyl-2-thpyrrolidone) ortegaserod at doses of 0.1, 0.3 and 1.0 mg/kg ip, respectively.Two subgroups of group C (C-Saline and C-Tegl.0) wereinjected with saline or tegaserod (1.0 mg/kg) ip. RD wasperformed 10 rain after injection, AWR was recorded andc-Fos expression in limbic system was analyzed quantitativelyby immunohistochemistry.RESULTS: Compared to saline, tegaserod significantlyinhibited AWR in group H (0.4 mL: from 2.0 to 0.5; 0.8 mL:from 3.5 to 1.5; 1.2 mL: from 4.0 to 3.0, P<0.01), but hadno significant effect on group C. Tegaserod dose-dependentlyattenuated the number of c-Fos positive neurons in limbicstructures, anterior cingulate cortex (ACC) showed thegreatest attenuation. In group H, tegaserod (1.0 mg/kg)resulted in a significant overall decrease to 57% of H-saline(283+41 vs 162+16, P<0.01), in ACC to 42% of H-saline(72+10 vs31+8, P<0.01). In group C, tegaserod (1.0 mg/kg)resulted in an overall decrease to 77% of C-saline (214+13vs 164+22, P<0.01), in ACC to 65% of C-saline (48+8 vs31+7, P<0.01).CONCLUSION: Tegaserod inhibits the response to rectaldistention in rats with visceral hypersensitivity and dose-dependently attenuates c-Fos expression in limbic system,especially in anterior cingulate cortex.展开更多
AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： norma...AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase展开更多
文摘AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawley rats randomlyreceived colonic irritation by acetic acid from postnatal day8 to d 21 as a visceral hypersensitive model (group H) or byintrarectal saline as a control group (group C). When theybecame adults, rectal distention (RD) was performed by aballoon (6F; Fogarty arterial embolectomy catheter; length,20 mm; diameter, 2 mm) which was rapidly inflated withincreasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 sat five-minute intervals. Five subgroups of group H (H-saline,H-vehicle, H-Teg0.1, H-Teg0.3 and H-Tegl.0) were injectedrandomly with saline, vehicle (1-methyl-2-thpyrrolidone) ortegaserod at doses of 0.1, 0.3 and 1.0 mg/kg ip, respectively.Two subgroups of group C (C-Saline and C-Tegl.0) wereinjected with saline or tegaserod (1.0 mg/kg) ip. RD wasperformed 10 rain after injection, AWR was recorded andc-Fos expression in limbic system was analyzed quantitativelyby immunohistochemistry.RESULTS: Compared to saline, tegaserod significantlyinhibited AWR in group H (0.4 mL: from 2.0 to 0.5; 0.8 mL:from 3.5 to 1.5; 1.2 mL: from 4.0 to 3.0, P<0.01), but hadno significant effect on group C. Tegaserod dose-dependentlyattenuated the number of c-Fos positive neurons in limbicstructures, anterior cingulate cortex (ACC) showed thegreatest attenuation. In group H, tegaserod (1.0 mg/kg)resulted in a significant overall decrease to 57% of H-saline(283+41 vs 162+16, P<0.01), in ACC to 42% of H-saline(72+10 vs31+8, P<0.01). In group C, tegaserod (1.0 mg/kg)resulted in an overall decrease to 77% of C-saline (214+13vs 164+22, P<0.01), in ACC to 65% of C-saline (48+8 vs31+7, P<0.01).CONCLUSION: Tegaserod inhibits the response to rectaldistention in rats with visceral hypersensitivity and dose-dependently attenuates c-Fos expression in limbic system,especially in anterior cingulate cortex.
基金Supported by Innovation and Technology Fund of the Hong Kong SAR Government(UIM/101)the National Hi-Tech 863 Program of the Ministry of Science and Technology of China,2003AA2Z2052
文摘AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase
