1.Effect of propofol on autophagy in rat heart during ischemia-reperfusion injury
Xiuru QI ; Chunliang WANG ; Ying WANG ; Jing CHEN ; Hongjie WANG
The Journal of Practical Medicine 2016;32(10):1580-1583
Objective To investigate the effect of propofol on autophagy in SD rat heart during myocar-dial ischemia-reperfusion (I/R) injury. Methods Twenty-one male SD rats were randomly divided into three groups as follows (n = 7): the sham operation group, in which rats underwent sham operation without tightening of the coronary artery sutures; the myocardial ischemia-reperfusion group , in which rats were induced by occlud-ing the left anterior descending coronary artery for 30 min , followed by 120 min reperfusion and 0.9% NaCl in-fusion at 3 mL/(kg·h) at 10 min before occluding the left anterior descending coronary artery; the myocardial ischemia- reperfusion- propofol group, in which rats underwent I/R and propofol infusion at 6 mg/(kg·h) at 10 min before occluding the left anterior descending coronary artery. Before tightening of the coronary artery, at 30 min post-tightening of the coronary artery and at 120 min post-reperfusion, HR、 LVSP and ± dp/dtmax of rats were recordedin each group. Atter 120 min post-reperfusion, the serum concentrations of cTnT was measured. The in-jured cardiac tissue was collected to investigate the ultrastructure change under the TEM and to determine the levels of mTOR and p-mTOR. Results No signifcant differences in HR, LVSP and ± dp/dtmax before tighten-ing of the coronary artery. But, at 30 min post- tightening of the coronary artery, compared with groupⅠ, the HR, LVSP and ±dp/dtmax were significantly decresed in groupⅡ and Ⅲ(P < 0.05). Then, at 2 h post-reper-fusion, compared with groupⅠ, the HR, LVSP, ±dp/dtmax and the level of p-mTOR were significantly de-creased, but the serum concentration of cTnT was significantly increased in groupⅡ(P < 0.05); but, compared with groupⅡ, the HR, LVSP, ± dp/dtmax and the level of p-mTOR were significantly increased, the serum concentration of cTnT and the level of mTOR were significantly decreased in group Ⅲ(P < 0.05). Conclusions These data suggest that propofol could heighten the level of p-mTOR, and attenuate the expression of mTOR dur-ing the myocardial ischemia-reperfusion injury in SD rats.
2.Combined inhibition of STAT3 and HIF-1α for enhancement of chemosensitivity in the model of human laryngeal squamous cacinoma in nude mice.
Xiuying LU ; Xiaoming LI ; Qi SONG ; Xiuru MA ; Lifeng JIA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2016;30(4):314-318
OBJECTIVE:
To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice.
METHOD:
Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3.
RESULT:
The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t₁ = 2.782, t₂ = 3.873, P < 0.05); The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t₁ = 6.140, t₂ = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, P > 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t₁ = 5.509, P < 0.01; t₂ = 3.422, P < 0.05; t₃ = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t₁ = 8.307, P < 0.01; t₂ = 3.736, P < 0.05; t₃ = 4.524, P < 0.01).
CONCLUSION
Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.
Animals
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Antineoplastic Agents
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pharmacology
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Carcinoma, Squamous Cell
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drug therapy
;
metabolism
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Cisplatin
;
pharmacology
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Drug Resistance, Neoplasm
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Hypoxia-Inducible Factor 1, alpha Subunit
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genetics
;
metabolism
;
Ki-67 Antigen
;
metabolism
;
Laryngeal Neoplasms
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drug therapy
;
metabolism
;
Mice
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Mice, Nude
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Neoplasms, Experimental
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drug therapy
;
metabolism
;
STAT3 Transcription Factor
;
genetics
;
metabolism
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Tyrphostins
;
pharmacology