Résumé
OBJECTIVE: To investigate the effect of Tongli Shuji acupuncture on the behavioristics, the percentage of cerebral infarct volume, and the expression of Jagged2 and Notch2 proteins in the hippocampus of the ischemic hemisphere in rats with permanent ischemia of the right middle cerebral artery, as well as the mechanism of Tongli Shuji acupuncture in improving ischemic cerebrovascular disease. METHODS: Sprague-Dawley rats were randomly divided into sham-operation group, model control group, medication group, routine acupuncture group, and Tongli Shuji group, with 10 rats in each group. The suture method was used to establish a model of permanent ischemia of the right middle cerebral artery. The rats in the medication group were given Citicoline (0.4 mg/kg) by gavage, those in the routine acupuncture group were given acupuncture at"Baihui"(GV20) and"Dazhui" (GV14) 15 minutes per day, and those in the Tongli Shuji group were given acupuncture at "Zhengying "(GB17), "Tianjing"(SJ10), and"Huantiao"(GB30) at the left side. The neurological deficit score was determined on days 1, 7, 14, 21 and 28 after surgery, the percentage of cerebral infarct volume was measured after treatment, and Western blot was used to measure the protein expression of Jagged2 and Notch2 in the right hippocampal tissue. RESULTS: Compared with the sham-operation group, the model control group had significant increases in the neurological deficit score on day 1 after surgery (P<0.001). Compared with the model control, medication and routine acupuncture groups, the Tongli Shuji group had significant reductions in the neurological deficit score on day 21 after surgery (P<0.01). Compared with the sham-operation group, the model control group had a significant increase in the percentage of cerebral infarct volume(P<0.05)．The Tongli Shuji group had a significant reduction in the percentage of cerebral infarct volume compared with the medication groups (P<0.05). Compared with the model control group, the routine acupuncture group had a significant increase in the expression of hippocapmal Jagged2(P<0.01)．Compared with the model control, medication and routine acupuncture groups, the Tongli Shuji group had significant increases in the expression of hippocampal Jagged2 and Notch2 (P<0.01). CONCLUSION: Acupuncture can improve the behavioral manifestations of neurological deficit in rats with permanent ischemia of the right middle cerebral artery. Tongli Shuji acupuncture can significantly up-regulate the protein expression of Jagged2 and Notch2 in the hippocampal tissue of the ischemic region, possibly by activating the Notch signaling pathway to exert a neuroprotective effect.
Résumé
Objective The objective of this study was to investigate the abnormal expression of Notch signaling pathway members in pancreatic cancer and its important effect on the development of pancreatic carcinoma. Methods Affymetrix gene expres-sion microarray was used to screen the differentially expressed members of Notch signal pathway in 10 cases of pancreatic carcinoma and its adjacent tissues,and verified by real-time quantitative PCR and Western blotting. The lentivirus expression vector carrying the siRNA fragment of Jagged 2(JAG2)gene was transfected into the pancreatic cancer primary cells to construct the JAG2 gene re-pression-expressing pancreatic cancer cell line. MTT,flow cytometry and Transwell assays were used to analyze cell proliferation, changes of cell cycle and invasive transfer capabilities. Results A total of 512 differentially expressed genes were detected by Affy-metrix gene expression microarray,including 419 up-regulated genes and 93 down-regulated genes. JAG2( up-regulated expres-sion 8. 20 times),NOTCH1(up-regulated expression 3. 74 times),HES1(up-regulated expression 3. 27 times),and NOTCH2(up-regulated expression 3. 16 times)were differentially expressed in Notch signaling pathway. The results of PCR and Western blotting were consistent with those of gene chip. The growth curves of JAG2 gene repressed pancreatic cancer cells and pancreatic cancer pri-mary cells were drawn by the standard OD490 value of d1-d5 by MTT assay. JAG2 gene repressor expression vector could signifi-cantly inhibit the proliferation of pancreatic cancer cells. The cell cycle analysis showed that the apoptosis and the arrested cell cycle at the S phase were significantly increased in pancreatic cancer cells with JAG2 gene repressor expression. The invasive ability was significantly reduced in JAG2 gene repressor expression pancreatic cancer cells(P<0. 05). Conclusion Some members of the Notch signaling pathway are significantly differentially expressed in pancreatic cancer tissues,and repression of this member can affect the growth,cell cycle,invasion and metastasis of pancreatic cancer cells.
Résumé
AIM:To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS: SD rats were randomly divided into normal control group (C group,n=15), solvent control group (S group,n=15) and monocrotaline model groups (M group,n=15).The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline (50 mg/kg).The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure ( mPAP) and right ventricular systolic pressure (RVSP) were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS:Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly (P<0.01).The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups (P<0.01).The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION:The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .