Protective effects of heat shock protein70 induced by geranylgeranylacetone in atrophic gastritis in rats.
OBJECTIVE
To investigate the effect of geranylgeranylacetone (GGA) on the progression of atrophic gastritis in rats and its potential mechanism.


METHODS
Atrophic gastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution, 60% ethanol, and 20 mmol/L deoxycholic acid for 24 weeks. Accompanied by the induction of atrophic gastritis, 200 mg/kg GGA was administered by oral gavage for 8 weeks (weeks 17-24). The histological changes in gastric mucosa were quantitated by the index of inflammation, the gastric mucosal thickness, and the amount of glands of 1 mm horizontal length in antrum. Endogenous heat shock protein (HSP)70 levels and distribution were determined by immunoblotting and immunohistochemistry in gastric mucosa.


RESULTS
GGA alleviated the pathological progression of atrophic gastritis with inflammation relief (inflammation index: 1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandular restoration (mucosal thickness and quantity of glands: 194.3 microm and 38.7 mm in the GGA group; 123.3 microm and 32.7 mm in the atrophic gastritis group; P<0.05). GGA significantly induced HSP70 synthesis (P<0.05). Moreover, quercetin, an inhibitor of HSP70 expression, aggravated the infiltration of inflammatory cells and glandular loss in the antrum.


CONCLUSIONS
GGA prevented the progression of atrophic gastritis in rats via the induction of HSP70 expression.
Liu
Wei-li
WL
Department of Gastroenterology and Zhejiang Key laboratory of Traditional Chinese Medicine (TCM), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310012, China.
Chen
Shu-jie
SJ
Chen
Yan
Y
Sun
Lei-min
LM
Zhang
Wei
W
Zeng
Ya-min
YM
Zhou
Tian-hua
TH
Si
Jian-min
JM
D000641:Ammonia / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000627:therapeutic use; D018450:Disease Progression; D004224:Diterpenes / Q000494:pharmacology*; D005757:Gastritis, Atrophic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D011794:Quercetin / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000033:anatomy & histology / Q000473:pathology
D000897:Anti-Ulcer Agents; D000975:Antioxidants; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D000641:Ammonia; D011794:Quercetin; C031049:geranylgeranylacetone