Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1β-induced coronary artery in-stent restenosis in pigs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.</p><p><b>METHODS</b>Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.</p><p><b>CONCLUSION</b>SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.</p>

Thyroid nodular diseases in the population indergoing medical examination and the analysis of its relative factors in Dalian City,Liaoning Province / 中国地方病学杂志

Objective To investigate the characteristics about the prevalence of thyroid nodules detected on color Doppler uhrasonography(US) in people residing in Dalian City who undergo regular physical examinations, as well as its relative factors. Methods All thyroid sonographic and questionair procedures were performed in the 6020 people above 18-year-old living in the four districts of Dalian City for at least 5 years, who were examined at the department of health medical center of Dalian Municipal Central Hospital from May 2006 to March 2007. Urinary iodine concentration was measured in 2039 healthy adults selected by age layers in our study population. Moreover, urinary iodine concentrations were determined in 220 children aged 8-10 years old who were randomly chosen from four communities (55 children per elementary school from each community). The analysis of logistic regression was conducted for the risk factors linked to thyroid nodules. Results The prevalence of thyroid nodules in the 6020 adults was 38.5%(2319/6020), in which nodules sized between 0.3 and up to 0.5 cm were found in 17.1% (1030/6020), and those above 0.5 cm in 21.4% (1289/6020). Ultrsonography revealed solitary nodules in 17.2% (1036/6020), multinodular goiter in 21.3% (1283/6020). Fifty-four point nine percent (1272/2319) thyroid nodules showed solid internal echographic structures, 30.2%(701/2319) mixed and 14.9%(346/2319). The thyroid nodule detected rate in female individuals was 46.1% (1102/2393), among whom multinodular goiter [59.1% (651/1102)] was more than solitary nodules[40.9(451/1102)] in female; while only 33.6%(1217/3627) of male were detected to have thyroid nodule, there was a difference between the genders (χ2=95,079,P<0.01). The mediam urinary iodine concentration(MUI) was 184.32 μg/L in children and 216.75 μg/L in the health adults, moreover, it was 216.55 μg/L and 217.00 μg/L in the people with thyroid nodules and those without nodules without a significant difference (P>0.05). The rate of thyroid nodules gradually increased with age(χ2=344.998, P<0.01). The occurance of thyroid nodules was significant associated with gender and age(P<0.01). Conclusions The nutritional iodine intake in the four communities of Dalian City are adequate. The prevalence of thyroid incidentalomas is relatively high in this group of people receiving medical examination.

Inhibitory effect and acting mechanism of Tongxinluo on IL-1beta-mediated coronary intimal hyperplasia and 5-hydroxytryptamine-induced coronary vasospasm in small swine / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism.</p><p><b>METHODS</b>The model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method.</p><p><b>RESULTS</b>Coronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05).</p><p><b>CONCLUSION</b>TXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.</p>

Effects of rapamycin on Rho-kinase and p27 mRNA expressions in a porcine coronary intimal proliferation model induced by interleukin-1beta / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of rapamycin on the expressions of Rho-kinase and p27 mRNA during vascular intimal proliferation in a porcine model of coronary stenosis induced by interleukin-1beta (IL-1beta).</p><p><b>METHODS</b>The proximal segments of LAD and LCX were wrapped with cotton mesh that had absorbed sepharose bead solution with or without IL-1beta. Selective coronary angiography was performed two weeks later and the animals were killed for collecting the samples for histopathology and RT-PCR analyzing of Rho-kinase and p27 mRNA.</p><p><b>RESULTS</b>The expressions of Rho-kinase and p27 mRNA could be visualized in normal coronary wall. The expression of Rho-kinase mRNA was significantly enhanced and the expression of p27 mRNA was significantly decreased during the process of intimal proliferation induced by IL-1beta. Rapamycin significantly inhibited the intimal proliferation, reduced the infiltration of inflammatory cells, reduced the expression of Rho-kinase mRNA and increased the expression of p27 mRNA.</p><p><b>CONCLUSIONS</b>The expression of Rho-kinase mRNA is upregulated and p27 mRNA downregulated in coronary artery stenosis induced by IL-1beta and these effects could be abolished by cotreatment with rapamycin.</p>

Upregulated Rho-kinase and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in a porcine coronary artery spasm model with interleukin-1beta / 中华心血管病杂志

<p><b>OBJECTIVE</b>Phosphorylation of myosin light chain (MLC) is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1beta.</p><p><b>METHODS</b>Segments of left coronary artery adventitia were surrounded by normal saline (n = 8) or IL-1beta agarose microne (n = 8) for 2 weeks. Vasospastic responses to intracoronary serotonin or histamine then studied at the saline or IL-1beta-treated site. The Rho-kinase mRNA expression in the treated site was measured by reverse transcription-polymerase chain reaction analysis (RT-PCR). The extent of phosphorylation of myosin-binding subunit of myosin phosphates (MBS, one of the major substrates of Rho-kinase) were quantified by Western blot analysis.</p><p><b>RESULTS</b>Intracoronary serotonin or histamine repeatedly induced coronary artery spasm and coronary arterial stenosis was evidenced at IL-1beta-treated site. Expression of Rho-kinase mRNA in IL-1beta-treated site was significantly increased compared to saline treated site (98.20% +/- 7.66% vs. 63.70% +/- 4.26%, P < 0.05). Western blot analysis showed that during the serotonin-induced contractions the extent of phosphorylation of MBS was also significantly increased in the spastic site (25,485 +/- 4745 vs. 6510 +/- 779, P < 0.05).</p><p><b>CONCLUSION</b>Rho-kinase upregulation at the spastic site and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in inducing vascular smooth muscle hypercontraction in this porcine model.</p>

Palmitic acid induces apoptosis in human hepatoma cell line, HepG2 cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of palmitic acid (PA) on human hepatocytes and its mechanism.</p><p><b>METHODS</b>We administered a mimic hyperlipidemia condition of 0.2-0.4 mmol/L PA to human hepatoma cell line, HepG2 cells. Cell viability was determined by Trypan blue staining. Cell cycle and early apoptosis were determined by propidium iodide and/or Annexin V staining, and the levels of Bcl-2 and Bax were analyzed by flow cytometry.</p><p><b>RESULTS</b>An inhibition of cell growth was observed at a dose- and time-dependent manner in HepG2 cells after the treatment of PA. An apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis significantly increased after the treatment of PA for 4 days. Bcl-2 level slightly decreased; in contrast, Bax level elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio.</p><p><b>CONCLUSION</b>PA may induce cell death on hepatocytes via mitochondria-mediated apoptosis by reducing the level of Bcl-2/Bax.</p>