Antisense RNA: the new favorite in genetic research / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Antisense RNA molecule represents a unique type of DNA transcript that comprises 19-23 nucleotides and is complementary to mRNA. Antisense RNAs play the crucial role in regulating gene expression at multiple levels, such as at replication, transcription, and translation. In addition, artificial antisense RNAs can effectively regulate the expression of related genes in host cells. With the development of antisense RNA, investigating the functions of antisense RNAs has emerged as a hot research field. This review summarizes our current understanding of antisense RNAs, particularly of the formation of antisense RNAs and their mechanism of regulating the expression of their target genes. In addition, we detail the effects and applications of antisense RNAs in antivirus and anticancer treatments and in regulating the expression of related genes in plants and microorganisms. This review is intended to highlight the key role of antisense RNA in genetic research and guide new investigators to the study of antisense RNAs.

Multiple factors contributing to lipopolysaccharide-induced reactivity changes in rabbit pulmonary artery / 生理学报

To explore the underlying mechanism(s) of pulmonary arterial hypertension in endotoxic shock, the roles of N-acetylcysteine (NAC), nitric oxide (NO) and carbon monoxide (CO) were investigated. Pulmonary arterial rings (3-mm width) were prepared from 24 rabbits. Lipopolysaccharide (LPS), after 7-hour incubation, decreased the endothelium-dependent relaxation response of the arterial ring (pre-contracted with phenylephrine) to acetylcholine (1 mumol/L), but did not affect the endothelium-independent relaxation response to sodium nitroprusside. The LPS effects were reduced by a concomitant incubation with the free radical scavenger (NAC), NO donor (L-arginine), and CO donor (hemin), respectively. On the other hand, the LPS effects were enhanced by applying heme oxygenase-1 (HO-1) inhibitor (zinc protoporphyrin) to block CO production. The response to acetylcholine changed from relaxation to contraction, however, the contractile response to phenylephrine increased significantly after pre-incubation with nitric oxide synthase (NOS) inhibitor (L-NAME) to block NO production, confirming the importance of CO and NO. These results show that LPS impairs endothelium-dependent relaxation of the pulmonary artery, which can be greatly reduced by the antioxidant, or by supplying with NO and CO. Thus, multiple factors are involved in this model of endotoxin-induced pulmonary hypertension.

Expression of heme oxygenase-1 induced by lipopolysaccharide in thoracic aortic and its effect on vascular reactivity / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of heme- heme oxygenase-1 (HO-1)-carbon monoxide(CO)-cyclic GMP (cGMP)on aortic vascular reactivity in endotoxemic rats and its molecular mechanism.</p><p><b>METHODS</b>By using isolated vascular ring tension detecting technique, cumulative responses of thoracic aortic rings (TARs)to phenylephrine (PE) were measured at 6 h after lipopolysaccharide administration. Effects on contractile responses to PE were measured under which the TARs were incubated with hemin (He, donor of CO), zinc-protoporphyrin-IX(ZnPP-IX, selective inhibitor of HO-1), or methylene blue (MB, inhibitor of guanylyl cyclase), respectively. The content of CO and the activity of HO-1 were measured. The protein and the gene expression of HO-1 were examined by Western blot and RT-PCR.</p><p><b>RESULTS</b>Contractile responses of TARs to cumulative doses of PE were depressed by pretreated with LPS. The hyporesponsiveness was partly reversed by incubation with ZnPP-IX and was restored to normal by incubation with MB in endotoxemic rats. Incubation with He could contribute to the vascular hyporeactivity. The content of CO, the activity and the protein and the gene expression of HO-1 were significantly increased in aorta of endotoxemic rats.</p><p><b>CONCLUSION</b>LPS could induce the HO-1 mRNA and the protein expression, the activity of HO-1 increase in aorta, lead to active the pathway of heme-HO-1-CO-cGMP, which is one of the important mechanisms of the vascular hyporeactivity in endotoxemic rats.</p>

Inhibitory effect of cholecystokinin-octapeptide on production of cytokines in the lung of endotoxic shock rats / 生理学报

To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in serum and lung of endotoxic shock (ES) rats induced by lipopolysaccharide (LPS) and investigate its signal transduction mechanism of p38 mitogen-activated protein kinase (MAPK), the changes in mean arterial pressure (MAP) were observed by using a polygraph in four groups of SD rats: group of LPS (8 mg/kg i.v.) induced ES, group of CCK-8 (40 microg/kg i.v.) pretreatment 10 min before LPS (8 mg/kg) administration, group of CCK-8 (40 microg/kg i.v.) only, and normal saline (control) group; the contents of proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in the lung and serum were assayed using ELISA kits; and p38 MAPK was detected by Western blot. The results showed that CCK-8 alleviated LPS-induced decrease in MAP of rats; compared with the control, LPS elevated the levels of TNF-alpha, IL-1 beta and IL-6 in serum and lung significantly, while CCK-8 significantly inhibited the LPS-induced increases in TNF-alpha, IL-1 beta and IL-6 in serum and lung. The activation of p38 MAPK in the lung of ES rats was enhanced by CCK-8 pretreatment. These results suggest that CCK-8 can alleviate the LPS-induced decrease in MAP of ES rats and exert an inhibitory effect on the overproduction of proinflammatory cytokines, and that p38 MAPK may be involved in its signal transduction mechanisms.

Endogenous carbon monoxide attenuates lung injury following ischemia-reperfusion in the hind limbs of rats / 生理学报

To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in the lung injury as assessed by lung histology, polymorphonuclear count, malondialdehyde content and wet-to-dry weight ratio following ischemia-reperfusion (I/R) of hind limbs, zinc protoporphyrin (ZnPP), an inhibitor of HO activity, was used, and the lung HO activity and blood carboxyhemoglobin (COHb) level were measured. The results showed that HO activity and COHb level were increased significantly and lung injury occurred after limb I/R. After administration of ZnPP, the lung injury was further aggravated while the HO activity and COHb level were significantly decreased. These findings suggest that upregulation of HO activity followed by subsequent CO production attenuates the lung injury induced by limb I/R in rats.

Effects of cholecystokinin octapeptide on rat cardiac function and the receptor mechanism / 生理学报

The aim of this study was to explore the effects of cholecystokinin octapeptide (CCK-8) on cardiac function and the receptor mechanism in anesthetized rats. The mean arterial pressure (MAP), heart rate (HR), the left ventricle systolic pressure (LVP) and the maximal/minimum rate of LVP (+/-LV dp/dt(max)) were measured. The results obtained are as follows. (1) Low dose of CCK-8 (0. 4 microgram/kg i.v.) caused tachycardia and slight increase in MAP, LVP and LV dp/dt(max) (P<0.01), while medium dose (4.0 microgram/kg i.v.) and high dose of CCK-8 (40 microgram/kg i.v.) elicited a bradycardia and marked increase in MAP, LVP and LV dp/dtmax (P<0.01). (2) Proglumide (1.0 mg/kg i.v.), a CCK-receptor (CCK-R) antagonist, significantly inhibited the pressor effects of CCK-8, whilst it reversed the bradycardic responses (P<0.01). (3) Using reverse transcription polymerase chain reaction (RT-PCR), CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) mRNA were expressed in myocardium of rats. The above results indicate that CCK-8 may enhance cardiac function in a dose-dependent manner and elicit a change in HR, which is likely induced by the activation of CCK-R on myocardium.