| Objectives:To investigate whether the expression of TNF-a was influenced by the intervention of PDTC(tetrahydropyrrole two sulfur formiate) in rats with Congestive heart failure.And to explore the nuclear factorκB(NF-κB) decrease the creation of TNF-a in central system to block the influence of central system on heart failure and to explore the new method of the treatment of heart failure.Methods:48 rats with 200±25g from the animal center of Shanxi Medical University were grouped randomly into 2 groups:one group was heart failure group with 24 rats and the other group was sham operation.Rats underwent surgery to induce HF by ligating the left anterior descending coronary artery,or the same surgery without ligating the vessel(SHAM).In both heart failure group and sham operation group,the 24 rats were randomly grouped into 2 small groups(each 12 rats):intervention group treated with PTDC(150 mg/kg daily in drinking water) and control group treated with drinking water alone.At 4 weeks,6 rats were anesthetized for hemodynamic measurements with catheter that inserted via the right carotid artery and advanced to the aorta,then advanced into the left ventricle for measurement of LV end-diastolic pressure(LVEDP).Mean arterial pressure(MAP) and heart rate(HR) were measured with polygraph,and then euthanized for collection of brain,heart,and lung tissues.The heart was harvested,the ventricles were separated,and the right ventricle was weighed.The lungs were also harvested and weighed wet.Right ventricular(RV) and lung weights were expressed as a function of body weight(BW).Other 6 irrigated with physiological saline +4% paraformaldehyde(each 500 ml) passed through intubation by left ventricle,then the brains were taken out and put into 4%paraformaldehyde to fix immediately,the paraffin sections were prepared for Immunohistochemistry dyeing.Results:1.Immunohistochemistry:TNF-a expression was negative(-) in PVN of sham-operated rats, while it was strongly positive(+++) in heart failure group,and located in the paraventricular nucleus neurons and glial cell cytoplasm,in scattered brownish yellow granules,but its expression was middle-positive(++) in the group of PDTC intervention,also In less brownish yellow granules.2.Hemodynamics Detection:There was no statistical significant difference in heart rate between the sham group and control group of HF(P＞0.05).there were significant differences among others(P＜0.05);there was no significant difference in mean arterial pressure(MAP),left ventricular pressure maximal rate(LV+ dp / dtmax) and left ventricular pressure largest decline rate(LV-dp/dtmax) between the two groups of the sham group(P＞0.05),there were significant differences among others(P＜0.05).compared with sham-operated group,MAP,LV + dp / dtmax,and LV-dp/dtmax have been decreased in HF group(P＜0.05), compared with sham-operated group,MAP,LV + dp / dtmax,and LV-dp/dtmax have decreased in HF group (P＜0.05),but they have been increased after the intervention of PDTC.③compared with the sham-operated group,there was a significant increase in LVEDP(P＜0.05) from HF group,The level of LVEDP was decreased significantly in PDTC group than in control group(P＜0.05),however was higher than in sham operation group.3.Right ventricle and lung wet weight and weight changes:①There was no statistical significant difference in RVRW between two sham operation groups(P＞0.05).there were significant differences among others(P＜0.05);compared with the sham-operated group,the level of RVRW was significantly higher than heart failure group(P＜0.05).the level of RVRW was lower in PDTC group than heart failure group but still higher than the sham-operated group (P＞0.05).②There was no statistical significant difference in Lung and weight index between two sham operation groups(P＞0.05).compared with the sham-operated group,the level of Lung and weight index was significantly higher than heart failure group(P＜0.05).the level of Lung and weight index was lower in PDTC group than heart failure group but still higher than the sham-operated group(P＞0.05).4.Western blot Testing:There was no statistical significant difference between two sham operation groups,compared with the sham-operated group,the expression of TNF-a was significantly higher in heart failure group(P＜0.05).The explession of TNF-a plotein was decreased in PDTC group than in control group,however was higher than in sham operation group level.Conclusion:PDTC can dccreasc the lcvcl of TNF-a in PVN by inhibiting NF-K B activity, thus rcducing the degrce of heart failure. Objectives: To investigate the expression of TNF-a in the heart and kidney in rats withischemia-induced HF,and to explore a new method to retard the process of heart failure.Methods: 18 rats with 200±25g from the animal center of Shanxi Medical University weregrouped randomly into 3 groups(n = 6): sham-operated group, heart failure group and interventiongroup. Rats underwent surgery to induce HF by ligating the left anterior descending coronaryartery, or the same surgery without ligating the vessel (SHAM) . intervention group treatedwith PTDC (150 mg/kg daily in drinking water) and control group treated with drinking wateralone. After 4 weeks, all rats were weighted, anaesthetized, and irrigated with physiological saline+4% paraformaldehyde (each 500 ml ) passed through intubation by left ventricle, then thehearts and kidneys were taken out and put into 4% paraformaldehyde to fix immediately, theparaffin sections were prepared for immunohistochemistry staining.Results:1.The TNF-a was negative in the cardiac tissue from the rats of the sham operation. But itoverexpressed in the heart failure group, plenty of brownish yellow granule showing in the crossstriation and intercalated disk. The expression of TNF-a became weak in the treated group. Thegranule became less and light.2.The TNF-a was negative in the renal tissue from the rats of the sham operation. But itoverexpressed in the heart failure group. Plenty of browish yellow granule can be seen in the renaltubular cytoplasm. The expressin of TNF-a became weak, and granule decreased obviously in thetreated group.Conclusion: The expression of TNF-a was negative in the sham-operated group, while it waspositive in HF group. It became weaker in treated group than untreated one which means PDTCcan reduce the degree of heart failure.PDTC can reduce the expression of TNF-a in the kidney by inhibiting the activity of NF-κB inheart failure diseases, and thus improve the renal function. |
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