Bin Lü1, Lu Zhang, Yi-Hong Fan, Yi Xu. 1. Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
Abstract
OBJECTIVE: To estimate the effect of teprenone on the expression of heat shock protein (HSP) 70 and c-fos in stomach following prednisolone ingestion. METHODS: Fifty male Sprague-Dawley rats were randomly into 5 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) for 7 days, and since the 4 th day undergoing fasting for 4 days; model control group, undergoing gastric perfusion of NS for 7 days, and since the 4 th day undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg for 4 days; and 3 model therapy groups, undergoing gastric perfusion with low, middle, and high dose of teprenone (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) for 7 days and undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg since the 4 th day. Twenty-four hours after the last administration of drugs, the rats were killed with their stomachs taken out. The gastric ulcer index (UI) was measured. HE staining was used to observe the injury index of the gastric mucosa. The mRNA expression of HSP70 in the gastric tissue was semi-quantitatively detected with reverse transcription-polymerase chain reaction. The protein expression of c-fos in the gastric tissue was detected with immunohistochemical staining. RESULTS: The injury index of the gastric mucosa of the model control group was 5.5, significantly higher than that of the normal control group (0, P = 0.000), and the injury indexes of the 3 teprenone groups were all significantly lower than that of the model control group dose-dependently (all P < 0.01). The UI of the model control group was 44.5, significantly higher than that of the normal control group (0, P = 0.000), and the UI values of the 3 teprenone groups were 32.5, 23.0, and 23.0 respectively, all significantly lower than that of the model control group dose-dependently (all P < 0.01). The expression value of c-fos of the model control group was 42 +/- 8, significantly higher than that of the normal control group (P < 0.01), and that expression values of c-fos of the 3 teprenone groups were all significantly lower than that of the model control groups dose-dependently (all P < 0.01). The expression value of HSP70 mRNA of the model control group was 0.22 +/- 0.03, significantly higher than that of the normal control group (0.04 +/- 0.02, P < 0.01), and the expression values of HSP70 mRNA of the 3 teprenone groups were 0.36 +/- 0.05, 0.41 +/- 0.09, and 0.49 +/- 0.05 respectively, all significantly higher than that of the model control group (all P < 0.01). CONCLUSION: Teprenone is Pretreatment with teprenone, beneficial cytoprotective agent of gastric mucosa, has a gastroprotective effect against steroid-induced mucosal damage to a certain extent with the mechanism related to c-fos and HSP70 l level in the gastric mucosa.
OBJECTIVE: To estimate the effect of teprenone on the expression of heat shock protein (HSP) 70 and c-fos in stomach following prednisolone ingestion. METHODS: Fifty male Sprague-Dawley rats were randomly into 5 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) for 7 days, and since the 4 th day undergoing fasting for 4 days; model control group, undergoing gastric perfusion of NS for 7 days, and since the 4 th day undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg for 4 days; and 3 model therapy groups, undergoing gastric perfusion with low, middle, and high dose of teprenone (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) for 7 days and undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg since the 4 th day. Twenty-four hours after the last administration of drugs, the rats were killed with their stomachs taken out. The gastric ulcer index (UI) was measured. HE staining was used to observe the injury index of the gastric mucosa. The mRNA expression of HSP70 in the gastric tissue was semi-quantitatively detected with reverse transcription-polymerase chain reaction. The protein expression of c-fos in the gastric tissue was detected with immunohistochemical staining. RESULTS: The injury index of the gastric mucosa of the model control group was 5.5, significantly higher than that of the normal control group (0, P = 0.000), and the injury indexes of the 3 teprenone groups were all significantly lower than that of the model control group dose-dependently (all P < 0.01). The UI of the model control group was 44.5, significantly higher than that of the normal control group (0, P = 0.000), and the UI values of the 3 teprenone groups were 32.5, 23.0, and 23.0 respectively, all significantly lower than that of the model control group dose-dependently (all P < 0.01). The expression value of c-fos of the model control group was 42 +/- 8, significantly higher than that of the normal control group (P < 0.01), and that expression values of c-fos of the 3 teprenone groups were all significantly lower than that of the model control groups dose-dependently (all P < 0.01). The expression value of HSP70 mRNA of the model control group was 0.22 +/- 0.03, significantly higher than that of the normal control group (0.04 +/- 0.02, P < 0.01), and the expression values of HSP70 mRNA of the 3 teprenone groups were 0.36 +/- 0.05, 0.41 +/- 0.09, and 0.49 +/- 0.05 respectively, all significantly higher than that of the model control group (all P < 0.01). CONCLUSION:Teprenone is Pretreatment with teprenone, beneficial cytoprotective agent of gastric mucosa, has a gastroprotective effect against steroid-induced mucosal damage to a certain extent with the mechanism related to c-fos and HSP70 l level in the gastric mucosa.