经典瞬时受体电位Ⅰ型通道（TRPC_1）在SHR左室肥厚发生发展中的作用
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摘要
左室肥厚(left ventricular hypertrophy, LVH)是高血压病的常见并发症，被视为是猝死、心力衰竭等心血管事件的独立危险因素。先前研究表明，在基因敲除和动脉缩窄的大鼠左室肥厚动物模型上，经典瞬时受体电位Ⅰ型通道(transientreceptor potential canonical type1channels, TRPC_1)参与了其LVH的发生发展。本研究采用自发性高血压大鼠(SHR)左室肥厚模型，首先动态研究不同周龄TRPC_1表达及SHR左室肥厚发生发展之间的关系，再研究TRPC_1通路下游信号分子：钙调磷酸酶(calcineurin, CaN)、激活T细胞核因子-3(nuclear factor of activated Tcells-3, NAFTC3)的表达变化，以期研究TRPC_1、CaN、NFATC_3表达在SHR左室肥厚发生发展过程中的作用；并研究替米沙坦(telmisartan, Tel)干预TRPC_1表达和环孢素A(cyclosporinA, CsA)抑制CaN后SHR左室肥厚的变化，进一步证实TRPC_1参与了SHR左室肥厚的发生发展。
第一部分不同周龄SHR左室TRPC_1表达的动态变化
目的：通过研究TRPC_1随SHR周龄增加的动态变化，探讨TRPC_1是否参与SHR左室肥厚的发生发展。
方法：32只雄性SHR为实验组，随机分为4周龄组、8周龄组、12周龄组、18周龄组等亚组(n=8)，相同周龄雄性Wistar-Kyoto (WKY)大鼠作为对照组(n=8)。分别测量收缩压(SBP)、体重(BW)、室间隔厚度(IVS)、左室后壁厚度(LVPW)。测定心脏质量(HW)和左心室质量(LVW)，并计算左室质量指数(LVMI)。Real-time PCR、免疫组化和western blot分别检测TRPC_1、CaN、NFATC_3的mRNA转录和蛋白表达。p-NFATC_3蛋白表达用western blot测定，计算p-NFATC_3/NFATC_3比值。
结果：
1血压：SHR组SBP随着周龄的增加而显著升高(ρ<0.05)，4周龄SHR组与WKY组SBP无明显差异性(ρ>0.05)，但8周龄起SHR组SBP均显著高于同周龄WKY组SBP(ρ<0.05)。
2左室肥厚：SHR组IVS、LVPW随着周龄的增加而增加(ρ<0.05)，4周龄SHR*:国家自然基金(81170143)和福建医科大学重大科研项目计划课题资助(09ZD010)组与WKY组IVS、LVPW分别相比无明显区别(ρ>0.05)，8周龄起SHR组IVS、LVPW分别显著高于同周龄的WKY组(ρ<0.05)。8周龄后SHR组LVMI分别明显高于同周龄的WKY组(ρ<0.05)。
3TRPC_1、CaN、NFATC_3表达的变化：SHR组左心室TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达随着周龄增加而增加，8周龄起SHR组均明显高于同周龄的WKY组(ρ<0.05)，但8周龄-18周龄SHR组的p-NFATC_3/NFATC_3比值明显低于的WKY组(ρ<0.05)。
结论：8周龄的SHR发生左室肥厚的改变并随周龄增加而加重；在SHR左室肥厚的发生与发展过程中，TRPC_1及其下游分子CaN、NFATC_3表达逐渐上调，说明TRPC_1与SHR左室肥厚的发生与发展相关。
第二部分干预TRPC_1和CaN的表达对SHR左室肥厚的影响
目的：研究替米沙坦和环孢素A干预后，SHR左室肥厚与左心室TRPC_1、CaN、NFATC_3的表达的变化，进一步探讨TRPC_1是否参与SHR左室肥厚的发生发展。
方法：8周龄雄性SHR随机分为5组(n=8)，分别为：SHR组、替米沙坦组(8mg/kg.d,T组)、氨氯地平组(10mg/kg.d, A组)、低剂量环孢素A组(1.25mg/kg.d, LC组)、高剂量环孢素A组(5mg/kg.d, HC组)。选8周龄雄性WKY大鼠作为对照组(n=8)。干预10周后，测定大鼠体重(BW)、收缩压(SBP)、室间隔厚度(IVS)、左室后壁厚度(LVPW)。测定心脏质量(HW)、左心室质量(LVW)、计算左室质量指数(LVMI)。Real-time PCR、免疫组化和western blot分别检测TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达。p-NFATC_3蛋白表达用western blot测定，计算p-NFATC_3/NFATC_3比值。
结果：
1血压：SHR组SBP显著高于WKY组(ρ<0.05)。与SHR组比较，T组和A组SBP显著降低(ρ<0.05)，LC组SBP无明显变化(ρ>0.05)，HC组SBP显著增高(225.58±6.92mmHg vs.211.65±8.43mmHg, ρ<0.05)。
2左室肥厚：SHR组IVS、LVPW明显高于WKY组(ρ<0.05)。与SHR组比较，T组和LC组IVS和LVPW分别显著降低(ρ<0.05)，A组和HC组IVS和LVPW无显著变化(ρ>0.05)。SHR组LVMI显著高于WKY组(ρ<0.05)。与SHR组比较，T组和LC组LVMI分别明显降低(ρ<0.05)，而A组和HC组LVMI无明显变化(ρ>0.05)。
3TRPC_1、CaN、NFATC_3表达的变化：SHR组左心室TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达分别显著高于WKY组(ρ<0.05)，而p-NFATC_3/NFATC_3比值显著低于WKY组(ρ<0.05)。与SHR组比较，T组TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达表达明显降低(ρ<0.05)，但p-NFATC_3/NFATC_3比值显著提高(ρ<0.05)，A组TRPC_1、CaN、NFATC_3mRNA转录与蛋白表达及p-NFATC_3/NFATC_3比值分别与SHR组相比无明显变化(ρ>0.05)。与SHR组比较，LC组TRPC_1、CaN、NFATC_3mRNA和蛋白表达下降(ρ<0.05)，p-NFATC_3/NFATC_3比值增高(ρ<0.05)，而HC对TRPC_1、CaN、NFATC_3mRNA转录与蛋白表达及p-NFATC_3/NFATC_3比值分别与SHR组相比无明显变化(ρ>0.05)。
结论：
1替米沙坦不但能降压、改善SHR左室肥厚，而且也能下调TRPC_1、CaN、NFATC_3表达；氨氯地平能降压，但不能抑制SHR左室肥厚，对TRPC_1、CaN、NFATC_3表达无影响，说明TRPC_1在SHR左室肥厚的发生与发展过程中起重要作用。
2低剂量环孢素A抑制CaN后，NFATC_3、TRPC_1表达下调，SHR左室肥厚改善，进一步说明TRPC_1可能参与了SHR左室肥厚的发生与发展；
Left ventricular hypertrophy (LVH) is a common complication of hypertensionand an independent risk factor for cardiovascular death and heart failure. Previousstudies have shown that transient receptor potential canonical type1channels (TRPC_1)was involved in the development of LVH in two rat models: transgenic mice andaortic banding rats. The goal of this present study was to investigate whether TRPC_1correlates with LVH in spontaneously hypertensive rats (SHR). Firstly, we studied therelationship between the LVH development and the expression of TRPC_1and itsdownstream signal molecule Calcineurin (CaN) and nuclear factor of activated Tcells-3(NFATC_3) in left ventricule of SHR aged from4weeks to18weeks. Secondly,TRPC_1decreased by Telmisartan and CaN inhibited by cyclosporine were respectivelyapplied to8-week-SHR for10weeks to further test if TRPC_1was a role in the processof LVH by detecting the change in LVH and expression of TRPC_1, CaN and NFATC_3on SHR.
Part1The dynamic expression of TRPC_1on the left ventricle ofSHR with different week
Objectives: To investigate whether TRPC_1is involved with development of LVH inSHR by determining the expression of TRPC_1on different week of SHR.
Methods: Male SHRs were randomly assigned to four groups as experiment groups:4-week-old group,8-week-old group,12-week-old group,18-week-old group(n=8).Male and age matched Wistar-Kyoto rats (WKY) were served as control grouprespectively (n=8). At each time point, rats were measured respectively for systolicblood pressure (SBP), body weight (BW), inter ventricular septum (IVS) and leftventricular posterior wall (LVPW). After the rats were sacrificed, the heart mass (HM), left ventricle mass (LVM) were measured and LVMI were calculatedrespectively. The mRNA transcription and protein expression of TRPC_1, CaN andNFATC_3in LV were determined respectively by real-time PCR, western blot andimmunohistochemistry. The protein expression of p-NFATC_3was examined bywestern blot, and the ratio of p-NFATC_3/NFATC_3was calculated.
Results:
1SBP: SBP of SHR was markedly increased with age (ρ<0.05). SBP was similar incomparison to SHR and WKY at4-week-old(ρ>0.05). The significant increase ofSBP was showed in SHR compared with age-matched WKY from8-week to18-weekof age (ρ<0.05).
2LVH: IVS and LVPW were remarkably increased in SHR with age (ρ<0.05).There was no significant difference in both SHR and WKY at4-week-old. IVS andLVPW in SHR aged from8-week-old were significantly higher than those inage-matched WKY (ρ<0.05).The LVMI in SHR was significantly higher than that inage-matched WKY from8-week to18-week of age (ρ<0.05).
3Expression of TRPC_1, CaN and NFATC_3: Both the mRNA transcription andprotein expression of TRPC_1, CaN and NFATC_3on left ventricle in SHR weresignificantly upregulated with age (ρ<0.05). The ratio of p-NFATC_3/NFATC_3in SHRfrom8-week to18-week was significantly lower than that in age-matched WKY(ρ<0.05).
Conclusions:8–week-old SHR shows LVH and it is aggravated with age. During theprogression of LVH in SHR, the expression of TRPC_1and its downstream signalmolecule CaN and NFATC_3are gradually increased in left ventricle. These resultssuggest that TRPC_1probably associates with the development of LVH in SHR.
Part2The influence of LVH by intervening the expressions ofTRPC_1and CaN in SHR
Objectives: To study LVH change and the expressions of TRPC_1,CaN and NFATC_3on LV in SHR intervened with Telmisartan and Cyclosporin A respectively for furtherexploring whether TRPC_1participates in the process of LVH in SHR.
Methods:8-week-old male SHR were randomized to five groups (n=8): SHR group,Telmisartan group (8mg/kg.d, T group), Amlodipine group(10mg/kg.d, A group), lowdose of Cyclosporin A group (1.25mg/kg.d, LC group), and high dose of CyclosporinA group(5mg/kg.d, HC group) respectively.8-week-old male WKY was served ascontrol group(n=8). After10-weeks of administration, all rats were measuredrespectively for SBP, BW and IVS and LVPW. After the rats were sacrificed, the HWand LVW of rats were examined for calculating LVMI. The mRNA transcription andprotein expression of TRPC_1, CaN and NFATC_3in LV were determined by real-timePCR, western blot and immunohistochemistry respectively. The expression ofp-NFATC_3was examined by western blot and the ratio of p-NFATC_3/NFATC_3wascalculated.
Results:
1SBP: SHR group showed a significantly higher SBP than WKY group (ρ<0.05).Compared with SHR group, SBP of T group and A group were significantly decreased(ρ<0.05). SBP of LC group was similar to SBP of SHR group (ρ>0.05), while SBP ofHC group was significantly increased compared with SBP of SHR group (225.58±6.92mmHg vs.211.65±8.43mmHg, ρ<0.05).
2LVH: Both IVS and LVPW in SHR group were notably higher than those inWKY group (ρ<0.05). In comparison to SHR group, IVS and LVPW in T group andLC group were significantly decreased respectively (ρ<0.05), but those in A groupand HC group had no significant change (ρ>0.05).When compared to SHR group,LVMI of T group and LC group were significantly decreased (ρ<0.05), but was notdifference in A group and HC group (ρ>0.05).
3Expression of TRPC_1, CaN and NFATC_3: Both the mRNA transcription and protein expression of TRPC_1, CaN and NFATC_3in SHR group were significantlyincreased when compared to those in WKY group (ρ<0.05), while the ratio ofp-NFATC_3/NFATC_3in SHR group was remarkably lower than that in WKY group(ρ<0.05). Compared to SHR group, both the mRNA transcription and proteinexpression of TRPC_1, CaN and NFATC_3in T group and LC group were significantlydecreased (ρ<0.05), but the ratio of p-NFATC_3/NFATC_3in T group and LC group wassignificantly increased (ρ<0.05). The mRNA transcription and protein expression ofTRPC_1, CaN and NFATC_3and the ratio of p-NFATC_3/NFATC_3in A group and HCgroup were respectively similar to those in SHR group(ρ>0.05).
Conclusions:
1Telmisartan not only reduces SBP， but also ameliorates LVH as well asdownregulates expressions of TRPC_1, CaN and NFATC_3in SHR.Amlodipine has anantihypertensive effect on SBP, but has no effect on LVH, and expressions of TRPC_1,CaN and NFATC_3in SHR. These results imply the involvement of TRPC_1in theprogression of LVH in SHR
2After CaN is inhibited by low dose of cyclosporin A, LVH is attenuated and theexpression of NFATC_3and TRPC_1on left ventricle in SHR are decreased, whichfurther shows the TRPC_1participation in the development of LVH in SHR.
第一部分不同周龄SHR左室TRPC_1表达的动态变化
目的：通过研究TRPC_1随SHR周龄增加的动态变化，探讨TRPC_1是否参与SHR左室肥厚的发生发展。
方法：32只雄性SHR为实验组，随机分为4周龄组、8周龄组、12周龄组、18周龄组等亚组(n=8)，相同周龄雄性Wistar-Kyoto (WKY)大鼠作为对照组(n=8)。分别测量收缩压(SBP)、体重(BW)、室间隔厚度(IVS)、左室后壁厚度(LVPW)。测定心脏质量(HW)和左心室质量(LVW)，并计算左室质量指数(LVMI)。Real-time PCR、免疫组化和western blot分别检测TRPC_1、CaN、NFATC_3的mRNA转录和蛋白表达。p-NFATC_3蛋白表达用western blot测定，计算p-NFATC_3/NFATC_3比值。
结果：
1血压：SHR组SBP随着周龄的增加而显著升高(ρ<0.05)，4周龄SHR组与WKY组SBP无明显差异性(ρ>0.05)，但8周龄起SHR组SBP均显著高于同周龄WKY组SBP(ρ<0.05)。
2左室肥厚：SHR组IVS、LVPW随着周龄的增加而增加(ρ<0.05)，4周龄SHR*:国家自然基金(81170143)和福建医科大学重大科研项目计划课题资助(09ZD010)组与WKY组IVS、LVPW分别相比无明显区别(ρ>0.05)，8周龄起SHR组IVS、LVPW分别显著高于同周龄的WKY组(ρ<0.05)。8周龄后SHR组LVMI分别明显高于同周龄的WKY组(ρ<0.05)。
3TRPC_1、CaN、NFATC_3表达的变化：SHR组左心室TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达随着周龄增加而增加，8周龄起SHR组均明显高于同周龄的WKY组(ρ<0.05)，但8周龄-18周龄SHR组的p-NFATC_3/NFATC_3比值明显低于的WKY组(ρ<0.05)。
结论：8周龄的SHR发生左室肥厚的改变并随周龄增加而加重；在SHR左室肥厚的发生与发展过程中，TRPC_1及其下游分子CaN、NFATC_3表达逐渐上调，说明TRPC_1与SHR左室肥厚的发生与发展相关。
第二部分干预TRPC_1和CaN的表达对SHR左室肥厚的影响
目的：研究替米沙坦和环孢素A干预后，SHR左室肥厚与左心室TRPC_1、CaN、NFATC_3的表达的变化，进一步探讨TRPC_1是否参与SHR左室肥厚的发生发展。
方法：8周龄雄性SHR随机分为5组(n=8)，分别为：SHR组、替米沙坦组(8mg/kg.d,T组)、氨氯地平组(10mg/kg.d, A组)、低剂量环孢素A组(1.25mg/kg.d, LC组)、高剂量环孢素A组(5mg/kg.d, HC组)。选8周龄雄性WKY大鼠作为对照组(n=8)。干预10周后，测定大鼠体重(BW)、收缩压(SBP)、室间隔厚度(IVS)、左室后壁厚度(LVPW)。测定心脏质量(HW)、左心室质量(LVW)、计算左室质量指数(LVMI)。Real-time PCR、免疫组化和western blot分别检测TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达。p-NFATC_3蛋白表达用western blot测定，计算p-NFATC_3/NFATC_3比值。
结果：
1血压：SHR组SBP显著高于WKY组(ρ<0.05)。与SHR组比较，T组和A组SBP显著降低(ρ<0.05)，LC组SBP无明显变化(ρ>0.05)，HC组SBP显著增高(225.58±6.92mmHg vs.211.65±8.43mmHg, ρ<0.05)。
2左室肥厚：SHR组IVS、LVPW明显高于WKY组(ρ<0.05)。与SHR组比较，T组和LC组IVS和LVPW分别显著降低(ρ<0.05)，A组和HC组IVS和LVPW无显著变化(ρ>0.05)。SHR组LVMI显著高于WKY组(ρ<0.05)。与SHR组比较，T组和LC组LVMI分别明显降低(ρ<0.05)，而A组和HC组LVMI无明显变化(ρ>0.05)。
3TRPC_1、CaN、NFATC_3表达的变化：SHR组左心室TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达分别显著高于WKY组(ρ<0.05)，而p-NFATC_3/NFATC_3比值显著低于WKY组(ρ<0.05)。与SHR组比较，T组TRPC_1、CaN、NFATC_3mRNA转录和蛋白表达表达明显降低(ρ<0.05)，但p-NFATC_3/NFATC_3比值显著提高(ρ<0.05)，A组TRPC_1、CaN、NFATC_3mRNA转录与蛋白表达及p-NFATC_3/NFATC_3比值分别与SHR组相比无明显变化(ρ>0.05)。与SHR组比较，LC组TRPC_1、CaN、NFATC_3mRNA和蛋白表达下降(ρ<0.05)，p-NFATC_3/NFATC_3比值增高(ρ<0.05)，而HC对TRPC_1、CaN、NFATC_3mRNA转录与蛋白表达及p-NFATC_3/NFATC_3比值分别与SHR组相比无明显变化(ρ>0.05)。
结论：
1替米沙坦不但能降压、改善SHR左室肥厚，而且也能下调TRPC_1、CaN、NFATC_3表达；氨氯地平能降压，但不能抑制SHR左室肥厚，对TRPC_1、CaN、NFATC_3表达无影响，说明TRPC_1在SHR左室肥厚的发生与发展过程中起重要作用。
2低剂量环孢素A抑制CaN后，NFATC_3、TRPC_1表达下调，SHR左室肥厚改善，进一步说明TRPC_1可能参与了SHR左室肥厚的发生与发展；
Left ventricular hypertrophy (LVH) is a common complication of hypertensionand an independent risk factor for cardiovascular death and heart failure. Previousstudies have shown that transient receptor potential canonical type1channels (TRPC_1)was involved in the development of LVH in two rat models: transgenic mice andaortic banding rats. The goal of this present study was to investigate whether TRPC_1correlates with LVH in spontaneously hypertensive rats (SHR). Firstly, we studied therelationship between the LVH development and the expression of TRPC_1and itsdownstream signal molecule Calcineurin (CaN) and nuclear factor of activated Tcells-3(NFATC_3) in left ventricule of SHR aged from4weeks to18weeks. Secondly,TRPC_1decreased by Telmisartan and CaN inhibited by cyclosporine were respectivelyapplied to8-week-SHR for10weeks to further test if TRPC_1was a role in the processof LVH by detecting the change in LVH and expression of TRPC_1, CaN and NFATC_3on SHR.
Part1The dynamic expression of TRPC_1on the left ventricle ofSHR with different week
Objectives: To investigate whether TRPC_1is involved with development of LVH inSHR by determining the expression of TRPC_1on different week of SHR.
Methods: Male SHRs were randomly assigned to four groups as experiment groups:4-week-old group,8-week-old group,12-week-old group,18-week-old group(n=8).Male and age matched Wistar-Kyoto rats (WKY) were served as control grouprespectively (n=8). At each time point, rats were measured respectively for systolicblood pressure (SBP), body weight (BW), inter ventricular septum (IVS) and leftventricular posterior wall (LVPW). After the rats were sacrificed, the heart mass (HM), left ventricle mass (LVM) were measured and LVMI were calculatedrespectively. The mRNA transcription and protein expression of TRPC_1, CaN andNFATC_3in LV were determined respectively by real-time PCR, western blot andimmunohistochemistry. The protein expression of p-NFATC_3was examined bywestern blot, and the ratio of p-NFATC_3/NFATC_3was calculated.
Results:
1SBP: SBP of SHR was markedly increased with age (ρ<0.05). SBP was similar incomparison to SHR and WKY at4-week-old(ρ>0.05). The significant increase ofSBP was showed in SHR compared with age-matched WKY from8-week to18-weekof age (ρ<0.05).
2LVH: IVS and LVPW were remarkably increased in SHR with age (ρ<0.05).There was no significant difference in both SHR and WKY at4-week-old. IVS andLVPW in SHR aged from8-week-old were significantly higher than those inage-matched WKY (ρ<0.05).The LVMI in SHR was significantly higher than that inage-matched WKY from8-week to18-week of age (ρ<0.05).
3Expression of TRPC_1, CaN and NFATC_3: Both the mRNA transcription andprotein expression of TRPC_1, CaN and NFATC_3on left ventricle in SHR weresignificantly upregulated with age (ρ<0.05). The ratio of p-NFATC_3/NFATC_3in SHRfrom8-week to18-week was significantly lower than that in age-matched WKY(ρ<0.05).
Conclusions:8–week-old SHR shows LVH and it is aggravated with age. During theprogression of LVH in SHR, the expression of TRPC_1and its downstream signalmolecule CaN and NFATC_3are gradually increased in left ventricle. These resultssuggest that TRPC_1probably associates with the development of LVH in SHR.
Part2The influence of LVH by intervening the expressions ofTRPC_1and CaN in SHR
Objectives: To study LVH change and the expressions of TRPC_1,CaN and NFATC_3on LV in SHR intervened with Telmisartan and Cyclosporin A respectively for furtherexploring whether TRPC_1participates in the process of LVH in SHR.
Methods:8-week-old male SHR were randomized to five groups (n=8): SHR group,Telmisartan group (8mg/kg.d, T group), Amlodipine group(10mg/kg.d, A group), lowdose of Cyclosporin A group (1.25mg/kg.d, LC group), and high dose of CyclosporinA group(5mg/kg.d, HC group) respectively.8-week-old male WKY was served ascontrol group(n=8). After10-weeks of administration, all rats were measuredrespectively for SBP, BW and IVS and LVPW. After the rats were sacrificed, the HWand LVW of rats were examined for calculating LVMI. The mRNA transcription andprotein expression of TRPC_1, CaN and NFATC_3in LV were determined by real-timePCR, western blot and immunohistochemistry respectively. The expression ofp-NFATC_3was examined by western blot and the ratio of p-NFATC_3/NFATC_3wascalculated.
Results:
1SBP: SHR group showed a significantly higher SBP than WKY group (ρ<0.05).Compared with SHR group, SBP of T group and A group were significantly decreased(ρ<0.05). SBP of LC group was similar to SBP of SHR group (ρ>0.05), while SBP ofHC group was significantly increased compared with SBP of SHR group (225.58±6.92mmHg vs.211.65±8.43mmHg, ρ<0.05).
2LVH: Both IVS and LVPW in SHR group were notably higher than those inWKY group (ρ<0.05). In comparison to SHR group, IVS and LVPW in T group andLC group were significantly decreased respectively (ρ<0.05), but those in A groupand HC group had no significant change (ρ>0.05).When compared to SHR group,LVMI of T group and LC group were significantly decreased (ρ<0.05), but was notdifference in A group and HC group (ρ>0.05).
3Expression of TRPC_1, CaN and NFATC_3: Both the mRNA transcription and protein expression of TRPC_1, CaN and NFATC_3in SHR group were significantlyincreased when compared to those in WKY group (ρ<0.05), while the ratio ofp-NFATC_3/NFATC_3in SHR group was remarkably lower than that in WKY group(ρ<0.05). Compared to SHR group, both the mRNA transcription and proteinexpression of TRPC_1, CaN and NFATC_3in T group and LC group were significantlydecreased (ρ<0.05), but the ratio of p-NFATC_3/NFATC_3in T group and LC group wassignificantly increased (ρ<0.05). The mRNA transcription and protein expression ofTRPC_1, CaN and NFATC_3and the ratio of p-NFATC_3/NFATC_3in A group and HCgroup were respectively similar to those in SHR group(ρ>0.05).
Conclusions:
1Telmisartan not only reduces SBP， but also ameliorates LVH as well asdownregulates expressions of TRPC_1, CaN and NFATC_3in SHR.Amlodipine has anantihypertensive effect on SBP, but has no effect on LVH, and expressions of TRPC_1,CaN and NFATC_3in SHR. These results imply the involvement of TRPC_1in theprogression of LVH in SHR
2After CaN is inhibited by low dose of cyclosporin A, LVH is attenuated and theexpression of NFATC_3and TRPC_1on left ventricle in SHR are decreased, whichfurther shows the TRPC_1participation in the development of LVH in SHR.
引文
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