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Objective: To study whether the expression of heat shock protein 70 (HSP70) in lung tissue induced by GGA (geranylgeranylacetone) has a protective effect on radiation-induced lung injury in mice and its possible mechanism. Methods: One hundred and four health KM mice were randomly divided into control group, GGA group, radiation group and GGA combined with radiation group. Of GGA group and the GGA combined with radiation group before irradiation, the mice were pretreated with GGA at a dose of 600 mg·kg-1·d -1 for 3 d, while the mice of the control and the radiation groups were given 0.9% sodium chloride solution. Then the mice in the radiation group and the GGA combined with radiation group received whole-lung irradiation with X-ray at a single fraction of 20 Gy, while the mice of the other two groups received sham-irradiation. After irradiation, all the mice continued receiving treatment until the appropriate time points for detection. The expressions of HSP70 mRNA and TNF-α (tumor necrosis factor alpha) mRNA in lung tissues were detected by RT-PCR at day 1 and day 3 after irradiation. The positive cells and the distribution of HSP70 proteins were evaluated by immunohistochemistry at day 1 after irradiation. The morphological changes of lung tissues were observed by hematoxylin and eosin staining at day 3 and day 60 after irradiation. The pulmonary fibrosis severity was evaluated by Masson's trichrome staining and hydroxyproline content at day 60. The serum TGF-β1 (transforming growth factor- beta1) level at each time point was measured by ELISA. Results: The typical early stage radiation pneumonitis and the late pulmonary fibrosis were observed in mice in the radiation group. In mice treated by GGA and radiation, HSP70 expression level of the lung tissues was higher than that in the control group or the radiation group. TNF-α mRNA level, serum TGF-β1 level, the severities of radiation pneumonitis and pulmonary fibrosis, and the content of hydroxyproline in the GGA combined with radiation group were lower than those in the radiation group (P < 0.05). There was no significant difference between the GGA group and the control group for all indices. Conclusion: The expression of HSP70 in mice lung tissues induced by regular oral administration of GGA can protect against radiationinduced lung injury, which may be related to the inhibition of expressions of important inflammatory factor TNF-α and fibrosis-related factor TGF-β1. Copyright © 2012 by TUMOR.
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Background Retinal ischemia/reperfusion injury is a common pathological process in ophthalmology.It can cause permanent visual impairment.The prevention and treatment of retinal ischemia/reperfusion injury is one of the focus topics at home and abroad up to now.Objective Present study was to evaluate the protective effects of geranylgeranylacetone(GGA)on retinal ischemia/reperfusion injury.Methods The retinal ischemia/reperfusion models were established in 40 SD rats by the infusion of normal saline solution into the anterior ehamber to elevate the intraoeular pressure for 1 hour and then remove the process.GGA of 2 ml (800 ms/kg)was intragastrieally administered in 20 model rats as GGA group,and the equal volume of normal saline solution was used at the same way in other 20 models as model group.Four normal matched SD rats were served as normal control group.The histological changes of retina in 6,24,48,72 hours after modeling was examined by hematoxylin-eosin staining under the light microscope.and the expression of heat shock protein 70(HSP70)and caspase-3 in retina at the time points mentioned above was detected by immunohistochemistry.Results The edema of cornea and retina of rats appeared in 1 hour and peaked in 24 hours after modeling.In 72 hours after modeling,the edema was alleviated but the disorder of retina structure was found in model group.However,although the pathological change process was similar to that of model group,the damage of retina tissue was milder in the rats of GGA group under the light microscope.HSP70 and caspase-3 were absent in the retina of normal rats.But。The expression of HSP70 in retinal ganglion cells(RGCs)was found in 6 hours after modeling,reached peak in 24 hours and declined after that in model group.The numbers of positive cells for HSP70 in retina was significantly increased in various time points in GGA group,showing statistically significant differences between model group and GGA group(P<0.05).In model group,a few of caspase-3 positive cells were found 6 hours after reperfusion and increased gradually until reaching the peak 24 hours and then decreased gradually 48 hours later.Few caspase-3 positive cells were found 72 hour8 after reperfusion.The numbers of positive cells for caspase-3 decreased in GGA group compared with model group during the experimental duration with the considerable difference between these two groups(P<0.05).Conclusion GGA could protect RGCs against isehemia/reperfusion injury by upregulating the expression of HSP70 and downregulating the expression of caspase-3 in retina.
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AIM: To study the effects of geranylgeranylacetone(GGA) on the expression of heat shock protein70(HSP70) on retinal ganglion cells(RGC) in rats with chronic intraocular pressure(IOP) elevation.METHODS: Seventy Wistars were divided into blank control group(10 rats), chronic hypertension group(30 rats) and GGA group(30 rats). Chronic hypertension was created by cauterizing the superficial scleral veins. 800mg/(kg·d)GGA was given by oral daily after cauterization. Immunohistochemistry was used respectively to observe the changes of expression of HSP70 in the model rats and GGA interference rats at different time points during the course of chronic IOP elevation.RESULTS: The successful model was identified as the IOP over 40% of normal rats. The retinal thickness was significantly reduced in model group and model+ GGA group compared with normal rats from 21 days through 28 days after cauterization(P<0.05), and that of model rats was obviously decreased in comparison with model+ GGA rats(P<0.05). The number of ganglion cells was significantly decreased in model rats and model+ GGA rats compared with normal rats from 21 days and 28 days. The stronger expression intensity(IOD) value was seen for HSP70 in the model+ GGA rats by immunochemistry(P<0.01).CONCLUSION: Systemic administration of GGA protects retina from chronic IOP elevation by regulating the expression of HSP70.
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Objective To explore the protective effects of geranylgeranylacetone (GGA) on acute renal failure tats induced by isehemia reperfusion (IR) and the possible mechanism. Methods GGA (400 mg/kg) was administered to induce overexpression of heat shock protein 72 (HSP72) in the kidney of Sprague-Dawley (SD) rats. IR model was generated by temporary clamping the left renal artery for 45 minutes followed by right nephrectomy and 24 h reperfusion. A sham-operated group was used as normal control. 24 h after reperfnsion, rats were sacrificed. Blood was collected for measurement of serum creatinine (Scr) and blood urea nitrogen ( BUN ). Paraffin-embedded sections of the kidney were stained with PAS. Histological changes due to tubular damage were quantitated as tubular damage score. TUNEL assay was used to detect the apoptosis, and Western-blot was used to detect the expression of XIAP. Results After renal IR, the increased level of BUN and Scr, the tubular injury and the apoptosis of renal tubular epithelial cells were observed (P＜0.01). At the same time, the decreased level of XIAP was observed (P＜ 0.01). Compared with the control groups, the level of HSP72 expression was up-regulated in oral administration of GGA group (P＜0.05). The expression levels of BUN and serum creatinine were significantly decreased after IR injury in pre-conditioned rats with over-expression of HSP72 (P＜ 0.01 ). Kidney morphology was better preserved in GGA group. Rats with over-expression of HSP72 also revealed reduction of apoptotic cells by TUNEL stain and XIAP degradation by Western blot (P＜0.05). Conclusion GGA attenuates renal IR injury at least in part through inhibiting tubular cell apoptosis by decreasing XAIP degradation and restoring XIAP protein level.