Evaluation of cardiac safety of hydroxyrutaecarpine, hERG channel inhibitor / 药学学报

Drug-induced long QT syndrome (LQTS) has become an important clinical research topic, and the occurrence of acquired long QT syndrome (acLQTS) is mainly caused by drug inhibition of the human ether-α-go-go related gene (hERG) channel. The hERG gene encodes the α subunit of the fast-activating delayed rectifying potassium ion channel (Ikr), which plays an important role in the process of action potential phase 3 repolarization and is also the target of most antiarrhythmic drugs. The purpose of this study was to investigate the effect of hydroxyrutaecarpine (HRU) on the hERG channel and to evaluate its cardiotoxicity. The whole cell patch clamp technique was used to detect the effects of HRU on the current and kinetics of the hERG channel, and to confirm the binding site on the hERG channel. PCR was used to determine the effect of HRU on hERG mRNA expression. Western blotting was used to detect the effects of HRU on the expression of hERG protein and transcription factor Sp1. Immunofluorescence was used to confirm the effects of HRU on localization and expression of hERG protein and transcription factor Sp1. Studies have shown that transient HRU can inhibit hERG current and shorten the inactivation time constant. Its binding sites to the hERG channel are F656 and Y652. After incubation for 24 h, HRU can reduce the expression of hERG protein, inhibit the hERG current, reduce the level of hERG mRNA, and reduce the expression of transcription factor Sp1 in the nucleus and hERG protein in the cytoplasm. Immunofluorescence experiments also showed the same results suggesting that the inhibition of Sp1 expression by HRU is the cause of the decreased expression of hERG mRNA. In conclusion, the acute inhibition of HRU accelerates the channel inactivation process and reduces the inactivation time constant by binding to the F656 and Y652 sites in the hERG channel, thus reducing the hERG current. In addition, HRU also inhibits the expression of hERG protein, mainly by inhibiting the expression of transcription factor Sp1, the transcription function of hERG channel protein is down-regulated, so that the hERG protein is reduced.

[Health Risk Assessment of Tunnel Workers Based on the Investigation and Analysis of Occupational Exposure to PM10].

The health risk of tunnel workers' occupational exposure to PM10, was evaluated applying public health exposure evaluation nodel. A questionnaire survey of 250 tunnel workers was conducted in a construction site of Ma-zhu Highway in Hubei Province, and the concentrations of PM10 were monitored. The results showed that the PM10 exposure concentrations of different types of tunnel workers were extremely high. Compared with the limited value, the PM10 exposure concentrations were 83 times, 18 times, 8 times, 9 times Emd 9 times for excavation workers, blasting workers, supporting workers, slag-out workers and secondary-lining workers, respectively. For secondary-lining workers, the average daily exposure time was the longest, which was 11.48 h x d(-1), and the energy metabolism rate was also the highest, which was 1067.43 kj x (m2 x h)(-1). Regarding the inhalation rates, secondary-lining workers could be classified to high-level working intensity, and the other four types of tunnel workers could he classified to middle-level working intensity. The health risk assessment results showed that all tunnel workers had health risk. High exposure concentration of PM10 was the main reason for excavation workers' highest hazard quotient, and it was the same for the blasting workers. The reason for secondary-lining workers' high hazard quotient was that they had higher inhalation rates and longer average daily exposure time. In order to reduce the health risk of tunnel workers, firstly the workers should be equipped with appropriate respiratory protective equipment; secondly an appropriate tunnel working standard should be developed to set a reasonable working-years for reducing the exposure time.

Effect of earthworm decoction on airway inflammation of bronchial asthma in guinea pigs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Earthworm decoction on the airway inflammation of experimental bronchial asthma in guinea pigs and inquire into the mechanism in the decoction.</p><p><b>METHOD</b>Forty-eight guinea pigs were randomly divided into six groups: the control group, the model group, the dexamethasone group, the Xiaoqinglong decoction group, the earthworm decoction large dosage group and the Earthworm decoction low dosage group, 8 guinea pigs in each group. Except the control group, the other groups were sensitized with ovalbumin (OVA) by a combination of intraperitional injection and repeated intranasal challenges to establish the guinea pigs asthma model. However, in the control group, normal saline was used. The morphological changes of bronchial tube, the lung tectology and the inflammation germ cell quantity of eosinophils (Eos), lymphocytes (Ly), neutrophils (Neu) and total blood cells in the blood and bronchoalveolar lavaga fluid (BALF) were examinated in each group respectively.</p><p><b>RESULT</b>The levels of Eos, Ly, Neu and total cell quantity in the blood and BALF after the earthworm decoction treatment in the large dosage group were significantly lower than those in the model group (P <0.01), and in the low dosage group were lower too (P <0.05). The Earthworm decoction large dosage could obviously improve the bronchial tube epidermis damage, the mucous membrane gland proliferation and hydrops, asthma pathology change and basilar membrane accumulation. Eos apoptosis was obsered in the bronchoalveolar, blood and BALF. The Earthworm decoction small dosage had a similar effect but slightly to the large dosage.</p><p><b>CONCLUSION</b>The Earthworm decoction can lighten the airway inflammation in asthmatic guinea pigs, its mechanism is related with the inhibition of Eos infiltration, acceleration of Eos apoptosis and improvement of the bronchial tube and the lung tectology changes. The effect of the decoction is dose-dependent.</p>