5、The general anesthetic pentobarbital slows desensitization
and deactivation of the glycine receptor in the rat spinal dorsal
horn neurons (发表杂志:J Biol Chem, Vol. 277, 41369-41378)
Although many general acesthetics have
been found to produce anesthetic and analgesic effects by augmenting
GABAA receptor (GABAAR)function, the role of the glycine receptor
(GlyR) in this process is not fully understood at the neuronal
level in the spinal cord. We investigated the effects of a barbiturate
general anesthetic, pentobarbital(PB), on the glycinergic miniature
inhibitory postsynaptic currents(mIPSCs) and the responses to
exogenously applied glycine, or taurine, a low affinity GlyR
agonist, by using the whole-cell patchclamp technique in the
rat spinal dorsal horn neuros isolated using a novel mechanical
method. Bath application of 30 μM PB significantly prolonged
the decay time constant of the spontaneous glycinergic mIPSC
without changing its amplitude and frequency. Coapplication
of 0.3μM PB reduced the pead amplitude, affected the macroscopic
desensitization and deactivation of the response to externally
applied Gly in a concentration-dependent manner. In addition,
the recovery of Gly response from desensitization was also proonged
by PB. However, PB did not change the desensitization and deactivation
kinetics of the taurine-induced response. The GABAAR antagonist
bicuculline(10μM) did not affect the effect of PB on the Gly
response. Thus, PB ptolonged the sponal glycinergic mIPSCs by
slowing desensitization and deactivation of GlyR. Two other
structurally different intravenous anesthetics, i.e. prlpofol(10μM)
and etomidate (3μM), prolonged the duration of the glycinergic
mIPSC in the rat spinal dorsal horm neurons. In conclusion,
on GlyR-Cl- channel complexes there may exist action site(s)
of intravenous general anesthetics. GlyR and glycinergic neurotransmission
may play an important role in the modulation of general acesthesia
in the mammalian spinal cord.
作者:吕辉 (中国科技大学生命科学学院攻读硕士学位,师从徐天乐教授,专业特长:受体药理学)。
6、Correlation between a single nucleotide polymorphism in
the matrix metalloproteinase-2 promoter and risk of lung cancer
(发表杂志:Cancer Research, 2002,Vol. 62, 6430-6433)
Matrix metalloproeinases (MMPs) play
an important role in several steps of cancer development. A
single nucleotide polymorphism(-1306C→T)in the MMP2 promoter
sequence disrupts an Spl site and thus results in strikingly
lower promoter activity. Ww wxamined the relationship between
this polymorphism and risk for lung cancer in 781 cases and
852age-and sex-matched controls in a Chinese population. We
found that the allele frequency of MMP2-1306C was significantly
higher among cases than among controls (0.91versus 0.83). Subjects
with the CC genotype had an overall 2-fold increased risk for
developing lung cancer[adjusted odds ratio (OR)2.08; 95% confidence
interva (CI), 1.70-2.79]compared with those with the CT or TT
genotype. The elevated risk was observed evenly among different
subtypes of this cancer. Stratified analysis indicated an additive
interaction between the CC genotype and smoking on the elevated
risk. The ORs of lung cancer for the CC genotype, smoking, and
both factors combined were 2.38(95% CI 1.64-3.45), 4.26(95%CI
2.57-8.44), and 7.64(95%CI 4.74-12.33), respectively. Furthermore
,when the data were stratified by the pack-years smoked, this
joint effect was more evident and stronger in heavy smokers(OR
5.55,95%CI 3.34-9.22). these results demonstrate a significant
association between the MMP2-1306C/T polymorphism and risk of
developing lung cancer, solely or in a manner of interaction
with carcinogen exposure.
作者:于春媛 (中国协和医科大学攻读博士学位,师从林东昕教授,专业特长:肿瘤学)。
<<返回上一级