Expremion Of GRP78 And CHOP In Endoplamic Retlcum Of Rathemart Under The Strem And The Relations To Myocardial Reasape And The Intervention Of Drug On It

Background Hypertension, a vital syndrome, takes participation in thedevelopment of many kinds of diseases. Therefore, to reduce and even eliminatehypertension have an important clinical significance to the target organ. It hasbeen confirmed that hypertension seriously influences the function of heart,thereby leading to myocardial reshape and it is a vital risk factor on thedevelopment of cardiovascular diseases. But the mechenism on it is unclear yet.Studies show that myocardial reshape can be caused by hypertention,autoimmune cardiomyopathy, diabetic cardiomyopathy, abnormal vasoactivesubstances and ERS occurs on these pathological processes, indicating that ERSmay have relation to the initialzation and development of myocardial reshape.But the influence of noise stress on the hypertension and myocardial reshape ofrat and the relationship between noise stress and ERS are unclear yet. Calciuminoverload is an important induciable factor in myocardial apotosis. The release ofcalciumin from ER and its concentration in cytoplasm related to the death of cell via ERS. Study shows that most calcium channel blocker (CCB), Lacidipine forexample, can effectively reduce the myocardial apotosis in hypertension.However, if ERS is involved in the decrease of blood tention and myocardialapotosis by CCB drugs need to be further confirmed.In this study, noise stress hypertension rat model was established to observethe expression of glucose-regulated protein78 (GRP78), C/EBP homologousprotein (CHOP) in myocardial cells and the change of the structure and functionof hearts; to study the relation between hypertention and ERS and to explore themolecular mechenism of CCB reducing apotosis cells in hypertension, in theaim to provide novel theoretical evidences for preventing and controllinghypertension and finally find out new target of treatment.Hypertension model was established by breeding rats under noisycondition. Carotid intubation, B-ultrasound, immunohistochemistry andwestern-blot were used to assess (1) MAP, IVST, LPWT, EF value, E/A andLVWI; (2) the protein level of GRP78 and CHOP; (3) the change of cardiacmyocyte apotosis rate under the influence of noise; (4) the intervention effect ofCCB on the expression of GRP78, CHOP, on the apotosis of myocyte and thestructure and function of heart.Results: the MAP of 2w,4w,6w and 8w noise group was 142.32±8.89mmHg, 166.90±8.32 mmHg, 174.23±6.26 mmHg and 178.56±9.03 mmHgrespectively, and was significantly higher than the corresponding control group126.65±8.89 mmHg, 129.65±8.86 mmHg, 130.65±9.87 mmHg, 132.65±9.87mmHg respectively). The MAP was increased along the time; (2) the IVST andLPWT increased with time, among which, the IVST of 4W,6W and 8W noisegroup were 29%, 33% and 38% higher respectively than the correspondinggroups (p<0.05), and the LPWT of these groups were 29%, 29% and 33% higher respectively than the corresponding groups (p<0.05).(3) the LVWI of 2W,4W, 6W and 8W group were 23%, 23%, 30% and 26% higher than thecorresponding group (p<0.05). There was no significant difference between eachcontrol groups; (4) There was no difference of the EF value between 2W noisegroup and control group. However, the EF value and the E/A ratio of 4W, 6Wand 8W were lower than the correspongding control groups (P<0.05). (5) theexpression of GRP78 in 2W, 4W, 6W and 8W noise group (OD value:0.50±0.032, 0.81±0.035, 0.61±0.033 and 0.52±0.034) was significantly higherthan tah corresponding groups (OD value: 0.20±0.030, 0.22±0.028, 0.21±0.032and 0.23±0.031), and reach its peak at week 4; (6) the expression of CHOP wassignificantly higher in the 2W, 4W, 6W and 8W noise group than thecorresponding control groups (OD value 0.45±0.05, 0.50±0.05, 0.62±0.04,0.71±0.06 and 0.14±0.05, 0.15±0.06, 0.17±0.04, 0.19±0.05 respectively)(p<0.05). the expression increased with time and recched its peak at week 8; (7)the expression of GRP78 in 2W, 4W, 6W and 8W group was 0.51±0.03,0.76±0.03, 0.61±0.03 and 0.52±0.05, while the corresponding control group was0.26±0.06, 0.28±0.06, 0.29±0.04 and 0.27±0.05. the difference between eachnoise and control group was significant (p<0.01). The expression reached themaximum at week 4, then declined with time. (8) the expression of CHOP in 2W,4W, 6W and 8W group (0.26±0.03, 0.38±0.02, 0.49±0.04 and 0.61±0.03) washigher than the control group (0.17±0.02, 0.18±0.02, 0.22±0.03 and 0.23±0.02)(p<0.05). the protein level of CHOP increased with time and reached themaxium at week 8; (9) a small amount cell experience apotosis in both 2W noisegroup and the control group, but the apotosis ratio was much higher in the 2Wnoise group (11.72±0.82% VS 5.34±0.75%). The apotosis ratio in 4W, 6W and8W noise group ((15.92±0.74)%, (26.27±0.78)%, (33.56±0.80)%) was also higher than the corresponding control group ((12.16±0.69)%, 6W(13.29±0.73)%, 8W(18.22±0.83)%). The apotosis of myocyte increased with time and thehighest ratio appeared on week 8.(10)MAP of the control group, noise groupand noise + Lacidipine group is 118.65±9.84mmHg,174.23±6.26mmHg及139.23±8.14mmHg.MAP of noise + Lacidipine group higher than the control group, below noisegroup (p < 0.05).(11)Noise stress after 6w, noise group and noise + Lacidipinegroup compared with controls, IVST and PWT all have difference (p < 0.05).(12)Noise stress after 6w, GRP78 and CHOP expression and myocardial cellapoptosis rate of noise + Lacidipinehe group are higher than the control group,below noise group, and a statistically significant (p < 0.05).Conclusion: (1) noise stress can induce myocyte ERS. (2) ERS wasinvolved in the protective response and apotosis by inducing the expression ofGRP78 and CHOP. (3) CHOP overexpressed with the escalation of BP. ERSparticipate in this pathological proces and disturbance the homeostasis of ER inmyocyte. (4) CCB may protect the myocyte by reducing the level of ERS andapotosis of it. And the mechanism may refer to the inhabition of CHOP.Therefor, it can be concluded that noise can activate RES in myocyte. Theimbalance of expression between GRP78 and CHOP cause the damage ofcardiac myocyte, which then caused the change of hemodynamic. This may bethe mechanism in hypertension caused by noise. The inbalance of homeostasisin ERS may initiate the ERS-related apotosis pathway via CHOP, therebycaused myocyte remodeling. CCB (Lacidipine for example) can decrease thedegree of ERS and apotosis, therefore protect myocyte from death. However, theexact turning point of homostasis to apotosis of myocyte induced by ERS andthe molecular mechanism of Lacidipine decreasing ERS need to be futherstudied.apotosis of myocyte thereby decrease the BP effectively. While whether ERS participate in this process is not clear up to now.and increase the apoptosisand this kind of change also occures in the myocardial cells. Endoplasmicreticulum stress (ERS) is a kind of stress response in cell. It is a pathologyprocess in cell organ, which is caused by endoplasmic reticulum homeostasisunbalanced and physiological function on disorder because of some reasons.Many researches indicate: ERS play a important role in coronary disease,diabetes, and so on. But in the forming process of hypertension, the problemsthat if does ERS take effect on this process, and what is its mechanism are stillneeded to research.