Blotting; incidence of apoptosis in cardiomyocytes was determined by TUNEL and DNA agarose
gel electrophoresis. Results: Post-ischemic functional recovery of LVDP and ±dp/dtmax were
better in IH hearts. [Ca2+]i in cardiomyocytes from normoxic hearts gradually increased during
ischemia and kept at higher level during reperfusion. However, in cardiomyocytes isolated from
IH hearts, [Ca2+]i kept at lower level during ischemia and reperfusion. Glibenclamide and 5-
hydroxydecunoate respectively abolished this effect. However, they had no effects on nomoxic
myocytes. Pinacidil attenuated calcium overloading during ischemia and reperfusion in normoxic
myocytes, but had no effect on IH myocytes. IH up-regulated the baseline protein expression of a
particular fraction of PKC-_, _, _. Ischemia and reperfusion induced the particulate/cytosolic ratio
of PKC-_, _ in IH hearts was higher than those of normoxic hearts and the particulate/cytosolic
ratio of PKC-_ in IH hearts was higher than that of normoxic hearts during ischemia period.
Ischemia/reperfusion-induced apoptosis was significantly reduced in the IH group. After
ischemia/reperfusion, the expression of Bax in both cytosolic and membrane fractions were
decreased, and the expression of Bcl-2 in membrane fraction was upregulated in IH hearts.
Conclusions: The results indicated that KATP channels and PKC contributed to the
cardiaoprotection afforded by IH against ischemia/reperfusion injury. The elimination of calcium
overload might underlie the mechanism of cardioprotection. IH attenuated ischemia/reperfusion-
induced apoptosis via increasing the ratio of Bcl-2/Bax in membrane fraction. (The study was
supported by NSFC no_30393130)
307.
HYPOXIA/ISCHEMIA MODIFIES THE PROLIFERATION AND DIFFERENTIATION OF
NEURAL STEM CELLS (NSCS) THROUGH HIF SIGNAL PATHWAY . Lingling Zhu
1
,
Liying Wu
1
, Zhicheng Xiao
2
, Ming Fan
1
. Department of Brain Protection and Plasticity, Institute
of Basic Medical Sciences
1
, Department of Anatomy, Singapore General Hospital
2
.
Studies of some scientists and ours have been carried out on the fact that NSCs exits within a
"physiological hypoxic" environment of both embryonic and adult brains at 1-5% O2 levels.
Rodent, mutant mice and some NSCs cell line were employed with ischemia, intermittent and
continuous hypoxia as models. Cell culture, RT-PCR, immunostaining, FACS and gene chips
were used to detect the effects of hypoxia. The results showed that hypoxia could promote the
growth of NSCs and maintain its survival in vitro and increase the number of endogenous NSCs
in SVZ and DG. Further works showed that hypoxia may influence the differentiation of NSCs
and produce more neuron, especially more doparminergic neuron, and less glia. The effects of
hypoxia on other kind of stem cells were also investigated and briefly introduced as additional
evidences. Hypoxic induced factor-1 (HIF-1) signal pathway may play a mainly role in the
mechanism of these responses. However, experiments with HIF (-/-) mice and gene chips
suggested other signal pathway involved. At end of this review, we discussed the idea of
"physiological hypoxia" in vitro and the possibility of HIF-1 independent way. These works
should be helpful to understand the mechanism of neurogenesis and to clinic therapy of NSCs.
This work was supported by key grant of National Nature Science Foundation of China.
(30393130)
308.
EFFECTS OF IPTAKALIM ON EXPRESSION OF ATP-SENSITIVE POTASSIUM
CHANNEL PROTEIN OF PULMONARY ARTERY SMOOTH MUSCLES IN CHRONIC
HYPOXIC RATS. Wang Zhu-Xin
1
, Xie Weiping
2
, Wang Hong
3
, Hu Gang
1
. Department of
Pharmacology & Neurobiology, Nanjing Medical University, Nanjing, China
1
, Department of
Internal medicine, Nanjing Yuhua Hospital, Nanjing, China
2
, Department of Pulmonology, The
First Affiliated Hospital, Nanjing Medical University, Nanjing
3
.
Objectives: To explore the effects of Iptakalim, a novel ATP sensitive potassium (KATP)
channel opener, on the protein expression of subunits of KATP channels in the pulmonary artery
smooth muscles of rats with chronic hypoxic pulmonary artery hypertension. Methods: Rats were
fed in hypoxic and normobaric environment (10%±0.5% O2,8h/day and 6day/week) and divided
into: A control group (rats treated with ig NS 5.0ml/kg/day), a hypoxia group(hypoxic rats treated
