Mechanism of Wenxin Granule Inhibits Myocardial Cell Apoptosis After Myocardial Infarctionby Regulating Endoplasmic Reticulum Stress in Rats / 中国实验方剂学杂志

Objective:To explore the intervention effect of Wenxin granule on endoplasmic reticulum stress apoptosis pathway and its related mechanism in rats with myocardial infarction. Method:Ligating the left anterior descending coronary artery to establish the rat model， the rats were randomly divided into 5 groups， namely sham group， model group， betaloc group and low， high-dose Wenxin granule groups，10 in each group. The sham group and the model group were given 10 mL∙kg^-1∙d^-1 deionized water， the low， high-dose modified Wenxin groups were given 1.35， 2.7 g∙kg^-1∙d^-1 aqueous solution respectively， and the betaloc group was given 2.25 mg∙kg^-1∙d^-1 aqueous solution. After 14 days，the catheter method was used to detect the cardiac hemodynamics and hematoxylin-eosin staining （HE） was used to observe the pathological morphological changes. The levels of endoplasmic reticulum stress protein glucose regulatory protein 78（GRP78）， protein kinase R like endoplasmic reticulum kinase（PERK）， phosphorylated activated PERK（p-PERK）， activated transcription factor 6 （ATF6）， nuclear transcription factor X cassette binding protein（XBP1） and apoptosis protein C/EBP homologous protein（CHOP）， B cell lymphoma/leukemia-2（Bcl-2） and Bcl-2 associated X protein（Bax） were detected by Western blot. Deoxyribonucleotide end-transferase-mediated notch end labeling （TUNEL） was also used to detect the myocardial cell apoptosis. Result:Compared with control group， the levels of the maximum ascending rate of left ventricular pressure（+dp/dt_max）， the maximum descending rate of left ventricular pressure（-dp/dt_max） and the left ventricular systolic blood pressure（LVSP） were decreased significantly（<italic>P</italic><0.05），but the level of the left ventricular end diastolic blood pressure （LVEDP） was significantly increased（<italic>P</italic><0.05）. The expressions of GRP78， p-PERK， PERK， ATF6， XBP1， CHOP， Bax and apoptosis index were increased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01）， while Bcl-2/Bax and Bcl-2 were decreased significantly（<italic>P</italic><0.01） in model group. Compared with the model group， the levels of -dp/dt_max and Bcl-2 were increased significantly （<italic>P</italic><0.05），while the level of the apoptosis index was decreased significantly（<italic>P</italic><0.01） in low-dose Wenxin granule group. In high-dose Wenxin granule group， the levels of +dp/dt_max and -dp/dt_max were increased significantly（<italic>P</italic><0.05，<italic>P</italic><0.01）， the levels of endoplasmic reticulum stress pathway protein GRP78， p-PERK， PERK， ATF6， XBP1，apoptosis-related protein CHOP， Bax and apoptosis index were decreased significantly（<italic>P</italic><0.01）， but Bcl-2 and Bcl-2/Bax were increased significantly （<italic>P</italic><0.01）. Conclusion:Wenxin granule has effect in inhibiting excessive endoplasmic reticulum stress， reducing myocardial cell apoptosis and improving cardiac hemodynamics. Its molecular mechanism may be related to decrease the levels of GRP78， PERK， p-PERK， ATF6， XBP1， CHOP， Bax and increasing the expression of Bcl-2.

Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway / 中国中药杂志

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Effect of Yishen Daluo Decoction on the expression of PLP, Olig1, and Olig2 in mice with experimental autoimmune encephalomyelitis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Yishen Daluo Decoction (YDD) on the expression of protein lipoprotein (PLP), oligodendrocyte transcription factor 1 (Olig 1), and oligodendrocyte transcription factor 2 (Olig2) in mice with experimental autoimmune encephalomyelitis (EAE).</p><p><b>METHODS</b>Totally 40 mice were randomly divided into 4 groups, i.e., the normal group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 mice in each group. Each mouse in the model, CM, and WM groups was subcutaneously injected with 200 microL antigen emulsion (containing 150 micro g PLP139 -151 and 400 micro g H37RA) in two parts at the upper abdomen on the first day. 100 microLBordetella pertussis juice (containing 0. 6 x 10(6) Bordetella pertussis) was injected by caudal vein on the first and the third day. On the 7th day after modeling, each mouse in the normal group and the model group was intragastrically given normal saline (0. 1 mL/10 g). YDD (0. 2 g crude drug/10 g) was intragastrically given to mice in the CM group, and prednisone (0. 039 mg/10 g) was intragastrically given to mice in the WM group. All mice were intervened for 54 days. Changes of PLP, Olig1, and Olig2 in the brain tissue of EAE mice were detected by Western blot. Results The levels of PLP and Olig2 in the brain tissue of the model group were less than those of the normal group (P <0.05). Compared with the model group, the levels of PLP, Olig1, and Olig2 in the brain tissue increased in the CM group (P <0.05); the levels of PLP and Olig2 in the brain tissue increased in the WM group (P <0.05). Compared with the WM group, the level of Olig1 in the brain tissue increased in the CM group (P <0.05).</p><p><b>CONCLUSION</b>YDD could enhance remyelination by elevating the levels of Olig1 and Olig2 in the brain tissue of EAE mice.</p>

Alteration of ion channel gene expression profile in rat model of post-myocardial infarction heart failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the ion channel genes related with the genesis and development of heart failure after myocardial infarction through analyzing the differential gene expressions in non-infarcted myocardial tissues of post-myocardial infarction heart failure (PIHF) rat model, and that of normal rat, and the bio-informatics Stc-GO analysis on them.</p><p><b>METHODS</b>Rat model of PIHF was established by left anterior descending coronary artery ligation in six SD rats, and a control group with six sham-operative rats was set. Myocardial samples were taken in two batches from them (three rats in each group) at the heart failure formation stage and the stable stage (10 days and 8 weeks after operation) respectively. Total RNA extraction, probe preparation with reverse transcription, hybridization with double-channel cDNA microarray of rat's ion channel genes, and computerized differential gene expression screening were conducted, and Stc-GO functional clustering analysis was performed on the outcomes obtained to search out the GO sort of significance in them.</p><p><b>RESULTS</b>At 10 days after operation, 319 common differential expressed genes were found from the 746 target genes, all of them were up-regulated. At 8 weeks after operation, in the 276 differential expressed genes, 274 were up-regulated while the other two down-regulated. The up-regulated genes were those concerning receptors of various hormones, cytokines, neuro-hormones, growth factors and nuclear receptor, protein phosphorylase, G protein, various ion channels mediated by ligand or voltage, transport protein, receptor interfering protein, etc. The down-regulated genes concerning the potassium channel and transport protein, etc. Stc-GO analysis found that the six genes concerning adrenergic receptor kinase beta 1 (betaARK1), amiloride-sensitive cation channel 2 neuronal (Accn2), voltage-dependent calcium ion channel gamma subunit 1 (Cacng1), cyclic nucleotide gated channel alpha 1 (Cnga1), Glutamate receptor ionotropic kainite 2 (Grik 2) and neurotrophic tyrosine kinase receptor type 2 (Ntrk 2), were all the significantly up-regulated differential genes of the model group related with the sham-operative group, and all showed a down-regulating trend as time goes on, and four genes in them were validated by the RT-PCR test.</p><p><b>CONCLUSION</b>Ion channel genes concerning Accn2, Grik2, Ntrk2 and Cacng1 were up-regulated in PIHF, and its mechanism is waiting for further study.</p>